Download biomedica product listPulmonary arterial hypertension (PAH), also known as World Health Organization (WHO) Group 1 pulmonary hypertension, is a rare and worsening condition (1). It is a disease characterized by increased blood pressure in the arteries of the lungs, which can lead to heart failure if left untreated.
It involves damage to the lining of the blood vessels in the lungs and changes in the vessel structure. These changes cause increased pressure in the pulmonary arteries, higher resistance in the blood vessels, and eventually lead to failure of the right side of the heart (2).
NPPB (Natriuretic Peptide Precursor B) is the gene that encodes the precursor protein for B-type natriuretic peptide (BNP). It is an early-response gene that is activated in cardiac myocytes, particularly in the ventricles, in response to mechanical stress, volume overload, or hormonal and sympathetic stimuli (3). When NPPB is transcribed and translated, it produces a 134-amino acid preproBNP, which undergoes further processing to generate BNP and NT-proBNP, both important biomarkers used in diagnosing and managing heart failure and other cardiovascular conditions (2). NT-proBNP has no known biological function but, due to its longer half-life compared to BNP (70 minutes versus 22 minutes) (4) and greater stability during storage (5), it offers potential advantages for use as a biomarker in clinical settings (4, 5).
NT-proBNP – A Potential Biomarker of Pulmonary Hypertension
A recent study explored the pathophysiological changes in patients during hemodialysis and blood reinfusion in patients with kidney disease.
The NT-proBNP ELISA from BIOMEDICA was used to measure NT-proBNP plasma levels for the noninvasive estimation of pulmonary arterial pressure (PAP) patients with chronic kidney failure:
Pathophysiological changes in patients during hemodialysis and blood reinfusion predict potential development of hemodialysis reactions. Pethő ÁG et al., Ren Fail. 2025.
Abstract
Hemodialysis reactions (HDRs) are a type of hypersensitivity reactions (HSRs), such as complement activation-related pseudoallergy (CARPA) observed during nanoparticle infusions. Our study aimed to elucidate the mechanisms of human HDRs by focusing on hemodynamic and clinical chemistry changes of HSR-related or biocompatibility issues during human hemodialysis (HD) and the reinfusion of blood. Based on our recent animal experiments, we hypothesize that increased pulmonary arterial pressure (PAP), and increases in thromboxane B2 (TXB2) and complement 3a (C3a) plasma concentrations will likely manifest in, or at least predict, human HDRs during HD and blood reinfusion. To verify our hypothesis, we measured these parameters during high-flux HD in patients. Since direct PAP measurement was not possible, the plasma concentration of the N-terminal fragment of the brain natriuretic peptide (NT-proBNP) was determined for the noninvasive estimation of PAP. Our results show an increase in NT-proBNP and TXB2 during the reinfusion of extracorporeal blood. The plasma concentration of C3a increased in early HD already and remained elevated up to blood reinfusion. In conclusion, the observed changes in HSR-related parameters or biocompatibility issues in otherwise asymptomatic patients may suggest that a greater activation of these mechanisms could explain the development of human hemodialysis reactions.
NT-proBNP ELISA | SK-1204 – HIGHLIGHTS
- Convenient – ready -to-use reagents
- Flexible – can be run in every lab
- Two controls included
- TRUSTED – widely cited in over 140 publications
- REPRODICIBLE – rigorously validated following international quality guidelines
- Assay independently validated in saliva samples link
DISCOVER MORE: Protocol Booklet, Validation data file
Literature
- Rare but serious: pulmonary vascular disease around the world. Hjalmarsson C, Jose A, Poor H, Loureiro CMC, Stosor V, Pulido T, Krishnan M. JHLT Open. 2025 Jul 18;9:100327. doi: 10.1016/j.jhlto.2025.100327. PMID: 40808822; PMCID: PMC12345328.
- BNP/NT-proBNP in pulmonary arterial hypertension: time for point-of-care testing? Lewis RA, Durrington C, Condliffe R, Kiely DG. Eur Respir Rev. 2020 May 15;29(156):200009. doi: 10.1183/16000617.0009-2020. PMID: 32414745; PMCID: PMC9488846
- Biochemistry of the human B-type natriuretic peptide precursor and molecular aspects of its processing. Semenov AG, Seferian KR. Clin Chim Acta. 2011 May 12;412(11-12):850-60. doi: 10.1016/j.cca.2011.03.006. Epub 2011 Mar 21. PMID: 21396929.
- Synthesis, secretion, function, metabolism and application of natriuretic peptides in heart failure. Fu S, Ping P, Wang F, Luo L. J Biol Eng. 2018 Jan 12;12:2. doi: 10.1186/s13036-017-0093-0. PMID: 29344085; PMCID: PMC5766980.
- Amino-terminal pro-B-type natriuretic peptide: analytic considerations. Ordonez-Llanos J, Collinson PO, Christenson RH. Am J Cardiol. 2008 Feb 4;101(3A):9-15. doi: 10.1016/j.amjcard.2007.11.013. PMID: 18243867.
- Pathophysiological changes in patients during hemodialysis and blood reinfusion predict potential development of hemodialysis reactions. Pethő ÁG, Révész C, Mészáros T, Sáfár O, Rosivall L, Domán J, Szénási G, Gigacz T, Dézsi L. Ren Fail. 2025 Dec;47(1):2500662. doi: 10.1080/0886022X.2025.2500662. Epub 2025 May 6. PMID: 40328739; PMCID: PMC12057777.
Further reading
- NT-proBNP Levels in Hemodialysis Patients: Unrelated to Interdialytic Weight Gain, Limited in Detecting Left Ventricular Systolic Dysfunction, but May Identify Atrial Fibrillation. Divani M, Katsanaki K, Tziastoudi M, Makri P, Poulianiti C, Lykotsetas E, Balatsouka A, Stefanidis I, Eleftheriadis Kidney and Dialysis. 2026; 6(2):42.
- Dialysis for Chronic Kidney Failure: A Review. Flythe JE, Watnick S. JAMA. 2024 Nov 12;332(18):1559-1573. doi: 10.1001/jama.2024.16338. PMID: 39356511.
Study Reveals Reliable Measurement of NT-proBNP in Rats Using Biomedica ELISA Assay in Cardiac Overload Model
We are pleased to share insights from a recent publication: ” Platelet transfusion induces transfusion-associated circulatory overload in rats with myocardial infarction.” (1). This study provides valuable understanding of transfusion-related complications in cardiac injury models, with a particular focus on monitoring cardiac stress and overload.
Key Highlight: Reliable detection of rat NT-proBNP in a TACO rat model in anemic Wistar rats with myocardial infarction using the Biomedica ELISA.
Accurate Detection of NT-proBNP in Rats – A Cardiac Safety Biomarker
A key tool in this research was the accurate quantification of NT-proBNP, a well-established biomarker for cardiac stress and heart failure. The researchers employed the Biomedica ELISA assay, renowned for its sensitivity and specificity, to measure NT-proBNP levels in rat plasma samples.
Rat NT-proBNP ELISA (cat. no. BI-1204R)
- CONVENIENT: Low sample volume (10 µL/well), kit control included
- HIGHLY SENSITIVE: Limit of detection (LOD) 21 pg/mL
- QUICK RESULTS: Assay time 3.5 hours
- TRUSTWORTHY RESULTS: Reference values provided, click here
The use of the Biomedica ELISA assay enabled precise detection of NT-proBNP levels, providing robust data on cardiac function and overload following platelet transfusion.
Implications for Future Research
The successful application of the Biomedica Rat NT-proBNP ELISA assay in this context demonstrates its suitability for preclinical cardiac studies involving small animals. Researchers aiming to explore cardiac biomarkers in rat models can confidently utilize this assay to obtain reliable and meaningful data.
Interested in measuring NT-proBNP in your research?
- Explore the Biomedica ELISA assay and enhance your data accuracy today!
- Contact us (info@bmgrp.com or +43 1 29107 54 ) ) for your evaluation kit!
Accurate Detection of NT-proBNP in Rats – A Cardiac Safety Biomarker
CARDIAC SAFETY Biomarkers – preclinical toxicology testing
Related Products:
NT-proANP ELISA assay (cat. no. BI-20892)
- CONVENIENT – 10 µl / well, serum or plasma, kit control included
- TRUSTED – widely cited as cardiovascular safety biomarker in rats
- MULTI-USE – for human and non-human samples (high cross-reactivity between species)
BIOMEDICA’s NT-proANP ELISA kit (BI-20892) has been independently validated through preclinical toxicology testing in rats. Click here to view citations
Cross-laboratory analytical validation of the cardiac biomarker NT-proANP in rat
Specifically, a cross-laboratory analytical validation of the cardiac biomarker NT-proANP in rats was conducted.
Briefly, the assay was evaluated by the Predictive Safety Testing Consortium’s Cardiac Hypertrophy Working Group (PSTC—CHWG) across five laboratories in a comprehensive analytical assessment for rat samples. The results demonstrated that the assay is robust and technically suitable for detecting NT-proANP serum levels in Sprague-Dawley rats.
Related Publications:
Evaluation of Cardiac Toxicity Biomarkers in Rats from Different Laboratories. Kim, K., Chini, N., Fairchild, D.G., Engle, S.K., Reagan, W.J., Summers, S.D., Mirsalis, J.C., 2016. Toxicol Pathol 44, 1072–1083. PMID: 27638646.
Serum Natriuretic Peptides as Differential Biomarkers Allowing for the Distinction between Physiologic and Pathologic Left Ventricular Hypertrophy . Dunn, M.E., Manfredi, T.G., Agostinucci, K., Engle, S.K., Powe J., King, N.M.P., Rodriguez, L.A, Gropp, K.E., Gallacher, M., Vetter, F.J., More, V., Shimpi, P., Serra, D., Colton, H.M., for The Cardiac Hypertrophy Working Group of the Predictive Safety Testing Consortium . 2017. Toxicol Pathol 45(2): 334-352. PMID: 27102652.
Natriuretic Peptides as Cardiovascular Safety Biomarkers in Rats: Comparison With Blood Pressure, Heart Rate, and Heart Weight . Engle, S.K., and Watson, D.E. 2016. Toxicol Sci 149: 458 – 472. PMID: 26609138.
2-Deoxy-d-Glucose (2-DG)-Induced Cardiac Toxicity in Rat: NT-proBNP and BNP as Potential Early Cardiac Safety Biomarkers. Terse PS, Joshi PS, Bordelon NR, Brys AM, Patton KM, Arndt TP, Sutula TP. Int J Toxicol. 2016 May;35(3):284-93. doi: 10.1177/1091581815624397. Epub 2016 Feb 2. PMID: 26838190; PMCID: PMC4864115.
also available: NT-proBNP ELISA (cat.no. SK-1204)
- Proficiency testing
- For human serum and plasma samples – saliva protocol
- Widely cited
NT-proBNP at Dialysis Initiation-Predictor of Heart Disease Hospitalization: Patients with end-stage kidney disease (ESKD) face a cardiovascular (CV) death risk approximately 10 to 20 times higher than that of the general population. Cardiac biomarkers serve as a valuable tool to predict CV morbidity and mortality in asymptomatic individuals.
About NT-proBNP
N-terminal pro-BNP (NT-proBNP) is a biomarker released by the heart in response to ventricular stretch and stress. It is commonly used to diagnose and manage heart failure, as elevated levels indicate cardiac dysfunction. NT-proBNP levels can also provide prognostic information regarding cardiovascular risk and outcomes in various conditions, including coronary artery disease, sepsis, and in patients with end-stage kidney disease (1).
NT-proBNP at Dialysis Initiation-Predictor of Heart Disease Hospitalization
A study by Shimohata H. et al, investigated if NT-proBNP measurement at the initiation of dialysis therapy is useful to predict later hospitalization for ischemic heart disease (IHD). The results demonstrated that NT-proBNP measurement at the initiation of dialysis therapy is useful to predict later hospitalization for IHD .
NT-proBNP was measured with the ELISA assay from BIOMEDICA
NT-proBNP ELISA assay kit (cat. no. SK-1204)
EASY – simple 2 step protocol, can be run in every lab
CONVENIENT – high and low kit controls included
RELIABLE – validated according to international quality guidelines (see validation data )
TRUSTED – widely cited in 140 publications
Related Products:
Rat NT-proBNP ELISA (cat. no. BI-1204R)
BNP Fragment EIA (cat. no. 20852W)
Literature
- NT-pro BNP level at dialysis initiation is a useful biomarker for predicting hospitalization for ischemic heart disease. Shimohata H, Usui J, Tawara-Iida T, Ebihara I, Ishizu T, Maeda Y, Kobayashi H, Numajiri D, Kaneshige A, Sega M, Yamashita M, Ohgi K, Maruyama H, Takayasu M, Hirayama K, Kobayashi M, Yamagata K; Study Group of the Ibaraki Dialysis Initiation Cohort Study. Clin Exp Nephrol. 2024 May;28(5):457-464. doi: 10.1007/s10157-023-02442-x.
- Association of NT-proBNP and BNP With Future Clinical Outcomes in Patients With ESKD: A Systematic Review and Meta-analysis. Harrison TG, Shukalek CB, Hemmelgarn BR, Zarnke KB, Ronksley PE, Iragorri N, Graham MM, James MT. Am J Kidney Dis. 2020 Aug;76(2):233-247. doi: 10.1053/j.ajkd.2019.12.017. Epub 2020 May 6. PMID: 32387090.
Abstract
Background: Patients with end-stage kidney disease (ESKD) are at high risk of cardiovascular disease including stroke, heart failure, and ischemic heart disease (IHD). To prevent the occurrence and progression of CVD, a reliable prognostic cardiac biomarker is essential. We investigated the prognostic value of NT-proBNP for each incident type of CVD.
Methods: Male patients from the Ibaraki Dialysis Initiation Cohort (iDIC) study with preserved serum samples from dialysis initiation day (n = 212) were analyzed. Patients were classified into four groups according to quartiles of baseline NT-pro BNP levels. The relationship between NT-proBNP levels at the initiation of dialysis and the subsequent incidence of hospitalization events due to IHD, heart failure, and stroke was analyzed.
Results: The incidence rate for hospitalization due to IHD was significantly higher in the highest NT-proBNP category (Log rank p = 0.008); those of stroke and heart failure showed no significant differences among quartiles. Cox proportional hazards regression analysis revealed that serum NT-proBNT was the only prognostic factor for hospitalization for IHD after adjustment by major known IHD risk factors. (HR, 1.008; 95% confidence interval, 1.002-1.014; p = 0.01) The ROC curve analysis for the incidence of hospitalization due to IHD showed that NT-proBNP had an area under the curve (AUC) of 0.759 (95% CI 0.622-0.897; p = 0.004) at a cut-off value of 956.6 pg/mL.
Conclusion: NT-proBNP measurement at the initiation of dialysis therapy is useful to predict later hospitalization for IHD.
We´re thrilled to share that our rat NT-proBNP ELISA kit (BI-1204R) was recently reviewed on Biocompare. The researchers stated “we are highly satisfied with the results, as we clearly observed clinically relevant rat NT-proBNP levels and the anticipated changes from baseline to completion.”
Read the review on Biocompare and click here:
-The good: Requires minimal sample volume, supports room temperature reactions, includes sufficient reagents for three runs in duplicate, and comes with a built-in control.
-The Bottom Line : A straightforward and easy-to-use kit with color-coded reagents, requiring only a small sample volume and room temperature incubations. Provides sufficient reagents for at least three runs in duplicate, and delivers clinically relevant data.
The investigators evaluated the impact of platelet transfusion on TACO development in a validated TACO rat model with heart failure.
Background:
- Transfusion-associated circulatory overload (TACO) accounts for 35% of transfusion-related fatalities.
- TACO after platelet transfusion has an increased mortality
Key findings:
- Platelet transfusion significantly increases Left Ventricular End-Diastolic Pressure (LVEDP)
- Platelet transfusion induces oxygenation impairment
- NT-proBNP is a biomarker supportive of TACO development
- Clinically, the results highlight the importance of cautious use of both plasma and platelet transfusions, particularly in high-risk patients
Figure: Rat NT-proBNP level changes in a preclinical model with myocardial infarction
Rat NT-proBNP – clinically relevant levels in TACO rat model
Platelet transfusion induces transfusion-associated circulatory overload in rats with myocardial infarction. Phelp PG et al.,Transfusion. 2025 Jul;65(7):1251-1263. PMID: 40384327.
Abstract
Background: Transfusion-associated circulatory overload (TACO) accounts for 35% of transfusion-related fatalities. Previous pre-clinical studies explored plasma and red blood cell transfusion in TACO, but the effect of platelets remains unexplored. Platelet transfusions have the highest rate of adverse reactions and are associated with increased mortality in TACO patients. We aimed to determine whether platelet transfusion induces circulatory overload compared to crystalloids and whether it causes a more severe phenotype than plasma in a TACO rat model of myocardial infarction (MI).
Methods: A validated TACO model in anemic Wistar rats with MI was used. Animals received platelets (n = 11), plasma (n = 10), or Ringer’s lactate (n = 11). Pulmonary capillary pressure was assessed via left-ventricular end-diastolic pressure (LVEDP). The primary outcome was the change in LVEDP (ΔLVEDP) following transfusion. Secondary outcomes included pulmonary wet/dry weight ratio, oxygen tension or partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio, and circulating biomarkers.
Results: LVEDP following platelet transfusion (10.4 ± 4.6 mmHg) was significantly greater than Ringer’s lactate (0.9 ± 1.4 mmHg; p < .001), but similar to plasma (13.0 ± 7.7 mmHg; p > .5). Pulmonary wet/dry weight ratios were comparable across groups (p > .5). At termination, PaO2/FiO2 ratio was significantly lower after platelet transfusion (372 ± 48) compared to Ringer’s Lactate (447 ± 79; p < .05). N-terminal prohormone of brain natriuretic peptide (NT-proBNP) did not differ between groups at termination (p > .1). However, NT-proBNP significantly increased from baseline (50 ± 24 pg/mL) to termination (177 ± 86 pg/mL) across all groups (p < .001).
Discussion: Platelet transfusion induces circulatory overload in a TACO rat model with heart failure when compared to crystalloids, showing a trend toward reduced oxygenation compared to plasma transfusion. Further investigation is needed to determine the pathophysiological mechanisms.
Rat NT-proBNP ELISA (cat. no. BI-1204R)
- Size: 12×8-well detachable strips
- Sensitivity: LOD: 21 pg/ml; LLOQ: 50 pg/ml
- Dynamic Range: 0 – 3200 pg/ml (0 / 100 / 200 / 400 / 800 / 1600 / 3200)
- Sample Type: rat serum, plasma
- Sample Size: 10 µL/well
- Assay time: 3.5 hours
- Protocol booklet – reference values provided (click here)
- Species: Rat
- Alternative Names: N-terminal pro-brain natriuretic peptide, NT-proBNP
- For Research Use Only
- Control included, color coded reagents
Product Citations:
–Circulating mitochondria carrying cGAS promote endothelial Secreted group IIA phospholipase A2-mediated neuroinflammation through activating astroglial/microglial Integrin-alphavbeta3 in subfornical organ to augment central sympathetic overdrive in heart failure rats. Zhang S, Huang Y, Han C, Chen M, Yang Z, Wang C. Int Immunopharmacol. 2025 Jan 10;144:113649. doi: 10.1016/j.intimp.2024.113649. Epub 2024 Nov 24. PMID: 39586230.
Snippet: C-1 (C2006), MitoTracker Green (C1048), and MitoTracker Red (C1049) were purchased from Beyotime (Shanghai, China). The rat NT-proBNP ELISA Kit (BI-1204R) and rat NE ELISA Assay Kit (EA633/96) were obtained from Eagle Biosciences (Amherst, NH, USA).
–Platelet transfusion induces transfusion-associated circulatory overload in rats with myocardial infarction. Phelp PG, Hurks B, Polet CA, Roelofs JJTH, Tuip-de Boer AM, Kapur R, Vlaar APJ, van den Brom CE, Klanderman RB.Transfusion. 2025 Jul;65(7):1251-1263. doi: 10.1111/trf.18285. Epub 2025 May 19. PMID: 40384327; PMCID: PMC12227162.
Snippet: N-terminal prohormone of brain natriuretic peptide (NT-proBNP; Cat# BI-1204R, Biomedica, Austria)
–Leucine Supplementation Improves Diastolic Function in HFpEF by HDAC4 Inhibition. Alves PKN, Schauer A, Augstein A, Männel A, Barthel P, Joachim D, Friedrich J, Prieto ME, Moriscot AS, Linke A, Adams V. Cells. 2023 Nov 2;12(21):2561. doi: 10.3390/cells12212561. PMID: 37947639; PMCID: PMC10648219.
Snippet: Blood serum was separated by centrifugation, and NT-proBNP levels were measured using RatNT-proBNP ELISA (Biomedica Immunoassays, Vienna, Austria) according to the manufacturer’s protocol.
Heart failure (HF) is a clinical condition caused by structural and/or functional abnormalities of the heart. Increased filling pressure in the heart´s left ventricle (LV) indicates diastolic dysfunction. The golden standard for diagnosis is the measurement of LV end-diastolic pressure (LVEDP) obtained through cardiac catheterization. However, this procedure is invasive. The objective of the following study was to explore the relationship between LVEDP and cardiac serum biomarkers, including including N-terminal prohormone B-type natriuretic peptide (NT-proBNP) and soluble ST2.
Natriuretic peptides and soluble ST2 improves echocardiographic diagnosis of elevated left ventricular filling pressures. Călburean Paet al., Sci Rep. 2024 Sep 27;14(1):22171. doi: 10.1038/s41598-024-73349-0. PMID: 39333652; PMCID: PMC11436802.
Abstract
Elevated filling pressure of the left ventricle (LV) defines diastolic dysfunction. The gold standard for diagnosis is represented by the measurement of LV end-diastolic pressure (LVEDP) during cardiac catheterization, but it has the disadvantage of being an invasive procedure. This study aimed to investigate the correlation between LVEDP and cardiac serum biomarkers such as natriuretic peptides (mid-regional pro-atrial natriuretic peptide [MR-proANP], B-type natriuretic peptide [BNP], and N-terminal prohormone BNP [NT-proBNP]), soluble ST2 (sST2), galectin-3 and mid-regional pro-adrenomedullin (MR-proAMD). Consecutive patients hospitalized in a tertiary center and undergoing left cardiac catheterization were included in the study. Diastolic dysfunction was considered present if the end-expiratory LVEDP was ≥ 15 mmHg. Cardiac biomarkers were determined from pre-procedural peripheral venous blood samples. A total of 110 patients were included, of whom 76 (69.0%) were males, with a median age of 65 (55-71) years. Median LVEDP was 13.5 (8-19) mmHg and diastolic dysfunction was present in 50 (45.4%) of the patients. LVEDP correlated with BNP (p < 0.0001, r = 0.39 [0.20-0.53]), NT-proBNP (p < 0.0001, r = 0.40 [0.22-0.55]), MR-proANP (p = 0.001, r = 0.30 [0.11-0.46]), sST2 (p < 0.0001, r = 0.47 [0.30-0.60]), but not with MR-proAMD (p = 0.77) or galectin-3 (p = 0.76). In the final stepwise multivariable binary logistic regression model, diastolic dysfunction was predicted by NT-proBNP, mitral average E/e’, sST2, atrial fibrillation, and left atrium reservoir strain. BNP, NT-proBNP, MR-proANP, and sST2 had predictive value for diastolic dysfunction. In contrast, galectin-3 and MR-proAMD were not associated with increased filling pressures. Furthermore, NT-proBNP and sST2 significantly improved diastolic dysfunction prediction in the final multivariable mode.
Diagnosis of Diastolic Heart Failure with NT-proBNP
NT-proBNP ELISA (cat. no. SK-1204)
√ CONVENIENT – can be used in every lab
√ RELIABLE – Full validation package
√ CE registered – for IVD use in EU
√ Widely cited in more than 130 publications
Cardiovascular disease is the leading cause of death in patients with end-stage renal disease on dialysis (1). In an attempt to understand the underlying mechanisms of the high mortality among dialysis patients, other than the traditional cardiovascular risk factors, researchers investigated the association between gut permeability, circulating bacterial fragments, and volume overload in peritoneal dialysis (PD) patients (2).
Gut permeability, circulating bacterial fragments and measures of congestion in peritoneal dialysis.
In this prospective observational study, 108 consecutive adult incident PD patients were recruited and circulating bacterial fragments, N-terminal pro B-type natriuretic peptide (NT-proBNP), calprotectin and zonulin levels were evaluated (2).
NT-proBNP in end-stage kidney disease
Markers of fluid overload
NT-proBNP is recognized as a marker of marker of left ventricular strain and intravascular fluid overload (3, 4).
Fluid overload was quantified by serum levels of NT-proBNP with the Biomedica ELISA kit (Biomedica-cat. no. SK-1204) and with multi-frequency bioimpedance spectroscopy (2).
NT-proBNP ELISA assay kit (cat. no. SK-1204)
√ CE-marked – for IVD use in the EU
√ EASY – simple 2 step protocol, can be run in every lab
√ High and low kit controls included
√ RELIABLE – validated according to international quality guidelines (see validation data )
√ TRUSTED – widely cited in 125 publications
Example of a Biomedica ELISA Assay Kit
Literature
1. Cardiovascular complications in chronic kidney disease: a review from the European Renal and Cardiovascular Medicine Working Group of the European Renal Association. Zoccali C, Mallamaci F, Adamczak M, de Oliveira RB, Massy ZA, Sarafidis P, Agarwal R, Mark PB, Kotanko P, Ferro CJ, Wanner C, Burnier M, Vanholder R, Wiecek A. Cardiovasc Res. 2023 Sep 5;119(11):2017-2032. doi: 10.1093/cvr/cvad083. PMID: 37249051; PMCID: PMC10478756.
2. Gut permeability, circulating bacterial fragments and measures of congestion in peritoneal dialysis. Li C, Ng JK, Chan GC, Fung WW, Lai KB, Poon PY, Luk CC, Chow KM, Szeto CC. Clin Kidney J. 2024 Mar 6;17(3):sfae056. doi: 10.1093/ckj/sfae056. PMID: 38516523; PMCID: PMC10956420.
3. NT-proBNP, fluid volume overload and dialysis modality are independent predictors of mortality in ESRD patients. Paniagua R, Ventura MD, Avila-Díaz M, Hinojosa-Heredia H, Méndez-Durán A, Cueto-Manzano A, Cisneros A, Ramos A, Madonia-Juseino C, Belio-Caro F, García-Contreras F, Trinidad-Ramos P, Vázquez R, Ilabaca B, Alcántara G, Amato D. Nephrol Dial Transplant. 2010 Feb;25(2):551-7. doi: 10.1093/ndt/gfp395. Epub 2009 Aug 12. PMID: 19679559.
4. Determination of volume overload by bioelectrical impedance analysis and NT-proBNP in diabetic pre-dialysis patients. Acta Endocrinol (Buchar). Yildirim Y, Kara AV, Kilinç F, Aydin F, Aydin E, Yilmaz Z, Kadiroglu AK, Yilmaz ME. 2016 Jan-Mar;12(1):19-25. doi: 10.4183/aeb.2016.19. PMID: 31258795; PMCID: PMC6586753.
Proficiency Testing is an external validation of diagnostic methods performed by accredited laboratories (1) as a measure to comply with international quality standards. Through participation in inter-laboratory comparisons such as proficiency testing programs, customers using a diagnostic method (e.g. an ELISA assay), can be assured that results generated from the assay comply with internationally set quality standards.
NT-proBNP assay successfully passes cardiac marker survey
NT-proBNP as a marker of heart failure
Heart failure is a significant cause of morbidity and mortality worldwide. Circulating biomarkers reflecting disease-related pathways that are involved in the development and progression of heart failure (HF) can be helpful in assisting clinicians in the early diagnosis and management of HF patients.
NT-proBNP (N-terminal pro B-type Natriuretic Peptide) is a cardiac protein fragment that is secreted into the bloodstream when the heart muscle stretches (under stress or damage). NT-proBNP is recognized as the hallmark biomarker for heart failure diagnosis and prognosis (2, 3).
NT-proBNP ELISA assay kit (cat. no. SK-1204)
- CE-marked – for IVD use in the EU
- Proficiency tested – click here to access the certificate
- Flexible – can be run in every lab
- Accurate – two controls included
- Easy – 2 step protocol
- Trusted – widely cited in 125 publications
Example of a Biomedica ELISA Assay kit
Developed & manufactured by Biomedica
Literature
- RfB- reference institute for bioanalytics– proficiency testing
- NT-proBNP: The Gold Standard Biomarker in Heart Failure. PM McKie PM and JC Jr Burnett. J Am Coll Cardiol. 2016; Dec 6;68(22):2437-2439. doi: 10.1016/j.jacc.2016.10.001. PMID: 27908348.
- Biomarkers for the diagnosis and management of heart failure. Castiglione V, Aimo A, Vergaro G, Saccaro L, Passino C, Emdin M.Heart Fail Rev. 2022 Mar;27(2):625-643. doi: 10.1007/s10741-021-10105-w. Epub 2021 Apr 14. PMID: 33852110; PMCID: PMC8898236.
November is recognized as Diabetes Awareness Month, raising attention about diabetes and the importance of prevention and management of the disease that impacts millions of people worldwide.
Diabetes and Heart Disease – Risk stratification with NT-proBNP
Diabetes and heart disease are closely linked and patients suffering from diabetes have a 2- to 4 fold increased risk for developing cardiovascular diseases (CVD) and concomitant heart failure (HF). Furthermore, HF patients with diabetes mellitus (DM) have a worse prognosis that those patients without DM (1, 2). In individuals with type 2 diabetes, high blood sugar levels and insulin resistance can lead to inflammation and atherosclerosis, a disease where arteries narrow, increasing the risk of CVD. Altered blood sugar levels are often associated with other CV risk factors, such as hypertension and obesity (3).
Diabetes and Heart Disease – Risk stratification with NT-proBNP
Identifying patients who are at risk in developing HF remains a clinical challenge. Assessing the risk of HF development in patients with diabetes is important and the use of biomarkers could be beneficial (4). NT-proBNP, a protein that is specifically secreted by cardiac cells, is the “gold standard” biomarker for heart failure (5, 6). In patients with type 2 diabetes, NT-proBNP has been shown to predict death and cardiovascular events (7, 8). Moreover, a recent study investigated the relationships of NT-proBNP with the risk of developing diabetes and diabetes-related complication in initially healthy individuals (9). NT-pro BNP levels were measured in blood samples in a large cohort (European Prospecive Investigation Into Cancer and Nutrition) of over 27,000 individuals. The study demonstrated that NT-proBNP concentrations were inversely associated with the risk of type 2 diabetes in healthy individuals. Higher NT-proBNP levels are related to a higher risk of vascular disease in people who develop the disease. The authors conclude that NT-proBNP may be a promising biomarker to identify asymptomatic individuals who are at high risk developing diabetes independent of potential confounders.
NT-proBNP can be reliably measured in SERUM & PLASMA with a conventional ELISA assay.
NT-proBNP ELISA assay highlights (cat. no. SK-1204)
- RELIABLE – CE marked – for IVD use in the EU
- FLEXIBLE & EASY– can be run in every lab
- CONVENIENT – Two controls included
- Assay independently validated in saliva samples
- Proficiency tested in accredited laboratory program Proficiency Testing Certificate
Example of a BIOMEDICA ELISA assay test kit.
NT-proBNP ELISA (#SK-1204) click here for more information
Related products
NT-proANP ELISA (cat. no. BI-20892) – for human and rodent samples (10µl sample volume)
Rat NT-proBNP ELISA (cat. no. BI-1204R) (10µl sample volume)
Literature
- Epidemiology, Pathophysiology, Diagnosis and Treatment of Heart Failure in Diabetes. Park JJ. Diabetes Metab J. 2021 Mar;45(2):146-157. doi: 10.4093/dmj.2020.0282. Epub 2021 Mar 25. Erratum in: Diabetes Metab J. 2021 Sep;45(5):796. PMID: 33813813; PMCID: PMC8024162.
- Diabetes as a risk factor for heart failure in women and men: a systematic review and meta-analysis of 47 cohorts including 12 million individuals. Ohkuma T, Komorita Y, Peters SAE, Woodward M. Diabetologia. 2019 Sep;62(9):1550-1560. doi: 10.1007/s00125-019-4926-x. Epub 2019 Jul 18. PMID: 31317230; PMCID: PMC6677875.
- Diabetes leading to heart failure and heart failure leading to diabetes: epidemiological and clinical evidence. Palazzuoli A, Iacoviello M. Heart Fail Rev. 2023 May;28(3):585-596. doi: 10.1007/s10741-022-10238-6. Epub 2022 May 6. PMID: 35522391; PMCID: PMC10140137.
- Assessing Cardiovascular Risk in Patients with Diabetes: An Update. Damaskos C, Garmpis N, Kollia P, Mitsiopoulos G, Barlampa D, Drosos A, Patsouras A, Gravvanis N, Antoniou V, Litos A, Diamantis E. Curr Cardiol Rev. 2020;16(4):266-274. doi: 10.2174/1573403X15666191111123622. PMID: 31713488; PMCID: PMC7903509.
- NT-proBNP: The Gold Standard Biomarker in Heart Failure. McKie PM, Burnett JC Jr. J Am Coll Cardiol. 2016 Dec 6;68(22):2437-2439. doi: 10.1016/j.jacc.2016.10.001. PMID: 27908348.
- 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: Executive Summary: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM, Deswal A, Drazner MH, Dunlay SM, Evers LR, Fang JC, Fedson SE, Fonarow GC, Hayek SS, Hernandez AF, Khazanie P, Kittleson MM, Lee CS, Link MS, Milano CA, Nnacheta LC, Sandhu AT, Stevenson LW, Vardeny O, Vest AR, Yancy CWCirculation. 2022 May 3;145(18):e876-e894. doi: 10.1161/CIR.0000000000001062. Epub 2022 Apr 1. PMID: 35363500.
- NT-proBNP as a predictor of death and cardiovascular events in patients with type 2 diabetes. Malachias MVB, Wijkman MO, Bertoluci MC. Diabetol Metab Syndr. 2022 May 3;14(1):64. doi: 10.1186/s13098-022-00837-6. PMID: 35501909; PMCID: PMC9063067.
- The role of NT-proBNP in the evaluation of diabetic patients with heart failure. Fringu FI, Sitar-Taut AV, Caloian B, Zdrenghea D, Comsa D, Gusetu G, Pop D. Acta Endocrinol (Buchar). 2020 Apr-Jun;16(2):183-191. doi: 10.4183/aeb.2020.183. PMID: 33029235; PMCID: PMC7535893.
- Opposing Associations of NT-proBNP With Risks of Diabetes and Diabetes-Related Complications. Birukov A, Eichelmann F, Kuxhaus O, Polemiti E, Fritsche A, Wirth J, Boeing H, Weikert C, Schulze MB. Diabetes Care. 2020 Dec;43(12):2930-2937. doi: 10.2337/dc20-0553. Epub 2020 Aug 17. PMID: 32816995; PMCID: PMC7770272.
NEW – Rat NT-proBNP ELISA assay
quantitative, reliable and robust for translational research and drug discovery.
Rat NT-proBNP ELISA assay │ BI-1204R
features & benefits
- 10 µl / well, serum or plasma
- kit control included
- sample values provided
NT-proANP ELISA assay │BI-20892
features & benefits
- 10 µl / well, serum or plasma
- widely cited as cardiovascular safety biomarker in rats
“cross-laboratory comparison study detecting serum NT-proANP in rats with the Biomedica NT-proANP ELISA to be technically adequate with acceptable intra- and inter-assay and inter-laboratory precision and accuracy (Vinken et al., 2016).”
All assays are developed and manufactured by Biomedica!
NT-proBNP & NT-proANP in drug-induced cardiac hypertrophy
The cardiac biomarkers NT-proBNP and NT-proANP are predictive of left ventricular hypertrophy (LVH) and systolic dysfunction in humans (1, 2).
In preclinical settings they have successfully been used to detect cardiotoxicity (3). NT-proBNP and NT-proANP have shown to be useful tools that help to improve the detection of cardiovascular injury early in drug development (4).
REFERENCES
- Circulating N-terminal pro-atrial natriuretic peptide is an independent predictor of left ventricular hypertrophy in the general population. The Tromsø Study. Schirmer H, Omland T. Eur Heart J. 1999 May;20(10):755-63. doi: 10.1053/euhj.1998.1396. Erratum in: Eur Heart J 1999 Oct;20(19):1439. PMID: 10329067.
- An association between N-terminal pro-brain natriuretic protein level and risk of left ventricular hypertrophy in patients without heart failure. Huang L, Huang L, Yu J, Wu X, Zhao J Exp Ther Med. 2020 May;19(5):3259-3266. doi: 10.3892/etm.2020.8598. Epub 2020 Mar 12. PMID: 32266021; PMCID: PMC7132238.
- Cardiac Hypertrophy Working Group of the Predictive Safety Testing Consortium. Serum Natriuretic Peptides as Differential Biomarkers Allowing for the Distinction between Physiologic and Pathologic Left Ventricular Hypertrophy. Dunn ME, Manfredi TG, Agostinucci K, Engle SK, Powe J, King NM, Rodriguez LA, Gropp KE, Gallacher M, Vetter FJ, More V, Shimpi P, Serra D, Colton HM Toxicol Pathol. 2017 Feb;45(2):344-352. doi: 10.1177/0192623316634231. Epub 2016 Jul 11. PMID: 27102652.
- Integrated approach to early detection of cardiovascular toxicity induced by a ghrelin receptor agonist. Stokes AH, Falls JG, Yoon L, Cariello N, Faiola B, Colton HM, Jordan HL, Berridge BR. Int J Toxicol. 2015 Mar-Apr;34(2):151-61. doi: 10.1177/1091581815573029. Epub 2015 Feb 26. PMID: 25722321.
Rat NT-proBNP ELISA kit | BI-1204R Highlights:
Compliance of NT-proBNP test in accredited cardiac marker survey
NT-proBNP ELISA test successfully passed accredited cardiac marker survey: Biomedica participated in an accredited international ring trial program for the cardiac biomarker NT-proBNP. The results demonstrate that the CE-marked NT-proBNP ELISA assay successfully passed the QC circle in the cardiac marker survey.
NT-proBNP ELISA test successfully passed cardiac marker survey
The results comply with strict quality standards confirmed by RfB, an international provider for proficiency testing.
NT-proBNP ELISA assay kit (cat. no. SK-1204)
√ CE-marked – for IVD use in the EU
√ Flexible – can be run in every lab
√ Two controls included
√ Simple 2 step protocol
√ Reliable – full validation
√ Widely cited in more than 100 publications
Developed & manufactured by Biomedica right in the heart of Europe
Biomedica Quality ELISA kits
What is proficiency testing?
Proficiency Testing provides a report that shows how laboratories can compare their own data to data to data from other laboratories around the world.
The testing, carried out in a ring trial program, is performed by an accredited laboratory specialist in proficiency testing. Proficiency testing monitors the performance of individual laboratories for specific tests e.g. cardiac biomarker assays.
LITERATURE
Monitoring of NT-proBNP – predicting risk of cardiovascular events from anti-inflammatory drugs (Non-Steroid Anti-Inflammatory Drugs)
N-terminal pro-B-type natriuretic peptide concentrations predict the risk of cardiovascular adverse events from antiinflammatory drugs: a pilot trial. Brune K, Katus HA, Moecks J, Spanuth E, Jaffe AS, Giannitsis E. Clin Chem. 2008 Jul;54(7):1149-57. doi: 10.1373/clinchem.2007.097428. Epub 2008 May 1. PMID: 18451314.
Safety of Oral Non-Selective Non-Steroidal Anti-Inflammatory Drugs in Osteoarthritis: What Does the Literature Say? Cooper C, Chapurlat R, Al-Daghri N, Herrero-Beaumont G, Bruyère O, Rannou F, Roth R, Uebelhart D, Reginster JY.Drugs Aging. 2019 Apr;36(Suppl 1):15-24. doi: 10.1007/s40266-019-00660-1. PMID: 31073921; PMCID: PMC6509083.
Cardio-renal safety of non-steroidal anti-inflammatory drugs. Radi ZA, Khan KN. J Toxicol Sci. 2019;44(6):373-391. doi: 10.2131/jts.44.373. PMID: 31168026.
Abstract
Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely used therapeutic class in clinical medicine. These are sub-divided based on their selectivity for inhibition of cyclooxygenase (COX) isoforms (COX-1 and COX-2) into: (1) non-selective (ns-NSAIDs), and (2) selective NSAIDs (s-NSAIDs) with preferential inhibition of COX-2 isozyme. The safety and pathophysiology of NSAIDs on the renal and cardiovascular systems have continued to evolve over the years following short- and long-term treatment in both preclinical models and humans. This review summarizes major learnings on cardiac and renal complications associated with pharmaceutical inhibition of COX-1 and COX-2 with focus on preclinical to clinical translatability of cardio-renal data.
Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis. Trelle S, Reichenbach S, Wandel S, Hildebrand P, Tschannen B, Villiger PM, Egger M, Jüni P.BMJ. 2011 Jan 11;342:c7086. doi: 10.1136/bmj.c7086. PMID: 21224324; PMCID: PMC3019238.
Sleeve gastrectomy might improve the “natriuretic handicap” of severely obese individuals
NT-proBNP serum levels increase with surgical weight loss interventions: Natriuretic peptides, including BNP hormone (B-type natriuretic peptide) and its amino-terminal counterpart NT-proBNP play a crucial role in the regulation of cardiovascular and energy homeostasis. They decrease blood pressure and increase the degradation of lipids and energy expenditure in fat tissue. Furthermore, both hormones are used as biomarkers in clinical practice in the diagnosis of heart failure.
Several studies have demonstrated that obesity is associated with low circulating levels of NT-proBNP concentrations, a condition known as “natriuretic handicap” * . In the following publication, researchers have investigated the impact of two surgical weight loss interventions on NT-proBNP serum concentrations in obese individuals without clinical signs of heart failure. Their data support the idea that the “natriuretic handicap * ” of obese individuals can be improved with surgically-induced weight loss, especially sleeve gastrectomy.
Effect of various weight loss interventions on serum NT-proBNP concentration in severe obese subjects without clinical manifest heart failure. Hollstein T et al. 2021.
*condition of decreased BNP levels in obese patients has been termed “the natriuretic handicap ” ( B-type natriuretic peptide and obesity in heart failure: a mysterious but important association in clinical practice. Reinmann M and P Meyer. 2020.)
⇒ NT-proBNP serum concentrations were measured with the Biomedica NT-proBNP ELISA (cat.no. SK-1204)
NT-proBNP serum levels increase with surgical weight loss interventions –
Kit highlights
√ CE-marked – for IVD use in the EU
√ Flexible – can be run in every lab
√ Two controls included
√ Simple 2 step protocol
√ Reliable – full validation
√ Widely cited
Developed & manufactured by Biomedica – right in the heart of Europe
Hollstein T, Schlicht K, Krause L, Hagen S, Rohmann N, Schulte DM, Türk K, Beckmann A, Ahrens M, Franke A, Schreiber S, Becker T, Beckmann J, Laudes M. Sci Rep. 2021. 12;11(1):10096. doi: 10.1038/s41598-021-89426-7. PMID: 33980890; PMCID: PMC8115663.
Abstract
The B-type natriuretic peptide (BNP) hormone plays a crucial role in the regulation of cardiovascular and energy homeostasis. Obesity is associated with low circulating levels of BNP, a condition known as “natriuretic handicap.” Recent evidences suggest an altered expression of BNP receptors-both the signaling natriuretic peptide receptors (NPR)-A and the clearance NPR-C receptor-in adipose tissue (AT) as one of the putative causes of natriuretic handicap.
The current study aims at clarifying the molecular mechanisms behind the natriuretic handicap, focusing on NPR modulation in the AT of obese and control subjects.
The study enrolled 34 obese and 20 control subjects undergoing bariatric or abdominal surgery, respectively. The main clinical and biochemical parameters, including circulating BNP, were assessed. In visceral (VAT) and subcutaneous AT (SAT) samples, collected during surgery, the adipocytes and stromal vascular fraction (SVF) expression of NPR-A and NPR-C and the SVF secretion of interleukin 6 (IL-6) were determined. Both VAT and SAT from obese patients expressed a lower NPR-A/NPR-C ratio in adipocytes and the SVF secreted a higher level of IL-6, compared with the controls. Moreover, NPR-A/NPR-C ratio expressed by VAT and SAT adipocytes negatively correlated with body mass index, insulin, the Homeostasis Model Assessment of Insulin resistance, and IL-6 secreted by SVF, and the expression of the clearance receptor NPR-C, in both the VAT and SAT adipocytes, showed a negative correlation with circulating BNP.
Overall, insulin resistance/hyperinsulinemia and AT inflammation (ie, high level of IL-6) are the major determinants of the lower NPR-A/NPR-C ratio in adipocytes, thus contributing to the natriuretic handicap in obese subjects.
RELATED PUBLICATIONS
Gentili A et al., . Transl Res. 2017. 186:52-61. doi: 10.1016/j.trsl.2017.06.001. PMID: 28651075.
Abstract
The B-type natriuretic peptide (BNP) hormone plays a crucial role in the regulation of cardiovascular and energy homeostasis. Obesity is associated with low circulating levels of BNP, a condition known as “natriuretic handicap.” Recent evidences suggest an altered expression of BNP receptors-both the signaling natriuretic peptide receptors (NPR)-A and the clearance NPR-C receptor-in adipose tissue (AT) as one of the putative causes of natriuretic handicap.
The current study aims at clarifying the molecular mechanisms behind the natriuretic handicap, focusing on NPR modulation in the AT of obese and control subjects.
The study enrolled 34 obese and 20 control subjects undergoing bariatric or abdominal surgery, respectively. The main clinical and biochemical parameters, including circulating BNP, were assessed. In visceral (VAT) and subcutaneous AT (SAT) samples, collected during surgery, the adipocytes and stromal vascular fraction (SVF) expression of NPR-A and NPR-C and the SVF secretion of interleukin 6 (IL-6) were determined. Both VAT and SAT from obese patients expressed a lower NPR-A/NPR-C ratio in adipocytes and the SVF secreted a higher level of IL-6, compared with the controls. Moreover, NPR-A/NPR-C ratio expressed by VAT and SAT adipocytes negatively correlated with body mass index, insulin, the Homeostasis Model Assessment of Insulin resistance, and IL-6 secreted by SVF, and the expression of the clearance receptor NPR-C, in both the VAT and SAT adipocytes, showed a negative correlation with circulating BNP.
Overall, insulin resistance/hyperinsulinemia and AT inflammation (ie, high level of IL-6) are the major determinants of the lower NPR-A/NPR-C ratio in adipocytes, thus contributing to the natriuretic handicap in obese subjects.
Parcha V, Patel N, Kalra R, Suri SS, Arora G, Wang TJ, Arora P. J Am Heart Assoc. 2021 Apr 6;10(7):e018689. doi: 10.1161/JAHA.120.018689. PMID: 33754794; PMCID: PMC8174357.
Abstract
Background Obese patients have lower NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels.
The prognostic implications of achieving NT-proBNP levels ≤1000 pg/mL in obese patients with heart failure (HF) receiving biomarker-guided therapy are not completely known.
We evaluated the prognostic implications of obesity and having NT-proBNP levels (≤1000 pg/mL) in the GUIDE-IT (Guiding Evidence-Based Therapy Using Biomarker-Intensified Treatment in HF) trial participants. Methods and Results The risk of adverse cardiovascular events (HF hospitalization or cardiovascular mortality) was assessed using multivariable-adjusted Cox proportional hazard models based on having NT-proBNP ≤1000 pg/mL (taken as a time-varying covariate), stratified by obesity status. The study outcome was also assessed on the basis of the body mass index at baseline. The predictive ability of NT-proBNP for adverse cardiovascular events was assessed using the likelihood ratio test. Compared with nonobese patients, obese patients were mostly younger, Black race, and more likely to be women. NT-proBNP levels were 59.0% (95% CI, 39.5%-83.5%) lower among obese individuals. The risk of adverse cardiovascular events was lower in obese (hazard ratio [HR], 0.48; 95% CI, 0.29-0.59) and nonobese (HR, 0.32; 95% CI, 0.19-0.57) patients with HF who had NT-proBNP levels ≤1000 pg/mL, compared with those who did not. There was no interaction between obesity and having NT-proBNP ≤1000 pg/mL on the study outcome (P>0.10). Obese patients had a greater risk of developing adverse cardiovascular events (HR, 1.39; 95% CI, 1.01-1.90) compared with nonobese patients. NT-proBNP was the strongest predictor of adverse cardiovascular event risk in both obese and nonobese patients.
Conclusions On-treatment NT-proBNP level ≤1000 pg/mL has favorable prognostic implications, irrespective of obesity status. NT-proBNP levels were the strongest predictor of cardiovascular events in both obese and nonobese individuals in this trial.
Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01685840.
NT-proBNP associated with mortality in COVID-19 patients with no history of heart failure: The cardiac biomarker N-terminal pro-B-type natriuretic peptide (NT-proBNP) plays a central role in the diagnosis and management of heart failure (HF). A recent report in patients with COVID-19 and no HF history demonstrates that high admission NT-proBNP is associated with higher mortality and healthcare resources utilization. The authors conclude that preventive strategies may be required for these patients.
Learn more: Admission NT-proBNP and outcomes in patients without history of heart failure hospitalized with COVID-19. Link to full text.
Check out the Biomedica NT-proBNP ELISA (cat.no. SK-1204)
√ CONVENIENT – can be used in every lab
√ RELIABLE – Full validation package
√ CE registered – for IVD use in EU
√ HIGH QUALITY GUARANTEED
Yoo J, Grewal P, Hotelling J, Papamanoli A, Cao K, Dhaliwal S, Jacob R, Mojahedi A, Bloom ME, Marcos LA, Skopicki HA, Kalogeropoulos AP. ESC Heart Fail. 2021. 5:4278-4287. doi: 10.1002/ehf2.13548. Epub 2021 Aug 4. PMID: 34346182; PMCID: PMC8426942.
Aims: We examined the value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients admitted for coronavirus disease 2019 (COVID-19) without prior history of heart failure (HF) or cardiomyopathy. Methods and results: Retrospective cohort of consecutive adults (N = 679; median age 59 years; 38.7% women; 87.5% White; 7.1% Black; 5.4% Asian; 34.3% Hispanic) admitted with documented COVID-19 in an academic centre in Long Island, NY. Admission NT-proBNP was categorized using the European Society of Cardiology Heart Failure Association age-specific criteria for acute presentations. We examined (i) mortality and the composite of death or mechanical ventilation and (ii) out-of-hospital, intensive care unit (ICU)-free, and ventilator-free days at 28 days. Estimates were adjusted for confounders using a lasso selection process. Using age-specific criteria, 417 patients (61.4%) had low, 141 (20.8%) borderline, and 121 (17.8%) high NT-proBNP. Mortality was 5.8%, 20.6%, and 36.4% for patients with low, borderline, and high NT-proBNP, respectively. In lasso-adjusted models, high NT-proBNP was associated with higher mortality [hazard ratio (HR) 2.15; 95% confidence interval (CI) 1.06-4.39; P = 0.034] and composite endpoint rates (HR 1.66; 95%CI 1.04-2.66; P = 0.035). Patients with high NT-proBNP had 32%, 33%, and 33% fewer out-of-hospital, ICU-free, and ventilator-free days compared with low NT-proBNP counterparts. Results were consistent across age, sex, and race, and regardless of coronary artery disease or hypertension, except for stronger mortality signal with high NT-proBNP in women. Conclusions: In patients with COVID-19 and no HF history, high admission NT-proBNP is associated with higher mortality and healthcare resources utilization. Preventive strategies may be required for these patients.
Related publications:
Characterization of NT-proBNP in a large cohort of COVID-19 patients. Link to full text.
Caro-Codón J, Rey JR, Buño A, Iniesta AM, Rosillo SO, Castrejon-Castrejon S, Rodriguez-Sotelo L, Martinez LA, Marco I, Merino C, Martin-Polo L, Garcia-Veas JM, Martinez-Cossiani M, Gonzalez-Valle L, Herrero A, López-de-Sa E, Merino JL; CARD-COVID Investigators. Eur J Heart Fail. 2021. Mar;23(3):456-464. doi: 10.1002/ejhf.2095. Epub 2021 Feb 1. PMID: 33421281; PMCID: PMC8013330.
Abstract:
Aims: Extensive research regarding the association of troponin and prognosis in coronavirus disease 2019 (COVID-19) has been performed. However, data regarding natriuretic peptides are scarce. N-terminal pro B-type natriuretic peptide (NT-proBNP) reflects haemodynamic stress and has proven useful for risk stratification in heart failure (HF) and other conditions such as pulmonary embolism and pneumonia. We aimed to adequately characterize NT-proBNP concentrations using a large cohort of patients with COVID-19, and to investigate its association with prognosis. Methods and results: Consecutive patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and available NT-proBNP determinations, from March 1st to April 20th, 2020 who completed at least 1-month follow-up or died, were studied. Of 3080 screened patients, a total of 396 (mean age 71.8 ± 14.6 years, 61.1% male) fulfilled all the selection criteria and were finally included, with a median follow-up of 53 (18-62) days. Of those, 192 (48.5%) presented NT-proBNP levels above the recommended cut-off for the identification of HF. However, only 47 fulfilled the clinical criteria for the diagnosis of HF. Patients with higher NT-proBNP during admission experienced more frequent bleeding, arrhythmias and HF decompensations. NT-proBNP was associated with mortality both in the whole study population and after excluding patients with HF. A multivariable Cox model confirmed that NT-proBNP was independently associated with mortality after adjusting for all relevant confounders (hazard ratio 1.28, 95% confidence interval 1.13-1.44, per logarithmic unit). Conclusion: NT-proBNP is frequently elevated in COVID-19. It is strongly and independently associated with mortality after adjusting for relevant confounders, including chronic HF and acute HF. Therefore, its use may improve early prognostic stratification in this condition.
Related products:
- NT-proANP ELISA (cat.no. BI-20892) Link
- Neuropilin-1 (cat.no. BI-20409) Link ; NRP1 IN COVID-19 disease read more
NT-proBNP saliva analysis for heart failure assessment. Monitoring Heart Failure – SALIVA ANALYSIS of Cardiac Marker NT-proBNP
The cardiac marker NT-pro-brain natriuretic peptide (NT-proBNP) is considered as the gold standard biomarker for the diagnosis and monitoring of heart failure (HF). It is tested in blood samples by immunochemical methods. Saliva analysis has gained importance as an alternative non-invasive and efficient tool for the diagnosis of several diseases. A recent report investigated the use of the Biomedica ELISA assay for the determination of NT-proBNP in saliva samples collected from HF patients. First results highlight the potential role of saliva analysis for HF assessment through NT-proBNP monitoring.
Learn more: Determination and stability of N-terminal pro-brain natriuretic peptide in saliva samples for monitoring heart failure. Link to full text.
Bellagambi FG, Petersen C, Salvo P, Ghimenti S, Franzini M, Biagini D, Hangouët M, Trivella MG, Di Francesco F, Paolicchi A, Errachid A, Fuoco R, Lomonaco T. Sci Rep. 2021. 22;11(1):13088. doi: 10.1038/s41598-021-92488-2. PMID: 34158583.
Check out the Biomedica NT-proBNP ELISA
√ CONVENIENT – can be used in every lab
√ RELIABLE – Full validation package
√ CE registered – for IVD use in EU
√ HIGH QUALITY GUARANTEED
Abstract
Heart failure (HF) is the main cause of mortality worldwide, particularly in the elderly. N-terminal pro-brain natriuretic peptide (NT-proBNP) is the gold standard biomarker for HF diagnosis and therapy monitoring. It is determined in blood samples by the immunochemical methods generally adopted by most laboratories. Saliva analysis is a powerful tool for clinical applications, mainly due to its non-invasive and less risky sampling. This study describes a validated analytical procedure for NT-proBNP determination in saliva samples using a commercial Enzyme-Linked Immuno-Sorbent Assay. Linearity, matrix effect, sensitivity, recovery and assay-precision were evaluated. The analytical approach showed a linear behaviour of the signal throughout the concentrations tested, with a minimum detectable dose of 1 pg/mL, a satisfactory NT-proBNP recovery (95–110%), and acceptable precision (coefficient of variation ≤ 10%). Short-term (3 weeks) and long-term (5 months) stability of NT-proBNP in saliva samples under the storage conditions most frequently used in clinical laboratories (4, − 20, and − 80 °C) was also investigated and showed that the optimal storage conditions were at − 20 °C for up to 2.5 months. Finally, the method was tested for the determination of NT-proBNP in saliva samples collected from ten hospitalized acute HF patients. Preliminary results indicate a decrease in NT-proBNP in saliva from admission to discharge, thus suggesting that this procedure is an effective saliva-based point-of-care device for HF monitoring.
Related publications
NT-ProBNP levels in saliva and its clinical relevance to heart failure. Foo JY, Wan Y, Kostner K, Arivalagan A, Atherton J, Cooper-White J, Dimeski G, Punyadeera C. PLoS One. 2012;7(10):e48452. doi: 10.1371/journal.pone.0048452. PMID: 23119023. Full text link
Abstract: Current blood based diagnostic assays to detect heart failure (HF) have large intra-individual and inter-individual variations which have made it difficult to determine whether the changes in the analyte levels reflect an actual change in disease activity. Human saliva mirrors the body’s health and well being and ∼20% of proteins that are present in blood are also found in saliva. Saliva has numerous advantages over blood as a diagnostic fluid which allows for a non-invasive, simple, and safe sample collection. The aim of our study was to develop an immunoassay to detect NT-proBNP in saliva and to determine if there is a correlation with blood levels. Methods: Saliva samples were collected from healthy volunteers (n = 40) who had no underlying heart conditions and HF patients (n = 45) at rest. Samples were stored at -80°C until analysis. A customised homogeneous sandwich AlphaLISA((R)) immunoassay was used to quantify NT-proBNP levels in saliva. Results: Our NT-proBNP immunoassay was validated against a commercial Roche assay on plasma samples collected from HF patients (n = 37) and the correlation was r(2) = 0.78 (p<0.01, y = 1.705× +1910.8). The median salivary NT-proBNP levels in the healthy and HF participants were <16 pg/mL and 76.8 pg/mL, respectively. The salivary NT-proBNP immunoassay showed a clinical sensitivity of 82.2% and specificity of 100%, positive predictive value of 100% and negative predictive value of 83.3%, with an overall diagnostic accuracy of 90.6%. Conclusion: We have firstly demonstrated that NT-proBNP can be detected in saliva and that the levels were higher in heart failure patients compared with healthy control subjects. Further studies will be needed to demonstrate the clinical relevance of salivary NT-proBNP in unselected, previously undiagnosed populations.
Saliva diagnostics – Current views and directions. Exp Biol Med (Maywood). 2017 Mar;242(5):459-472. doi: 10.1177/1535370216681550. PMID: 27903834; PMCID: PMC5367650. Full text link
Abstract: In this review, we provide an update on the current and future applications of saliva for diagnostic purposes. There are many advantages of using saliva as a biofluid. Its collection is fast, easy, inexpensive, and non-invasive. In addition, saliva, as a “mirror of the body,” can reflect the physiological and pathological state of the body. Therefore, it serves as a diagnostic and monitoring tool in many fields of science such as medicine, dentistry, and pharmacotherapy. Introduced in 2008, the term “Salivaomics” aimed to highlight the rapid development of knowledge about various “omics” constituents of saliva, including: proteome, transcriptome, micro-RNA, metabolome, and microbiome. In the last few years, researchers have developed new technologies and validated a wide range of salivary biomarkers that will soon make the use of saliva a clinical reality. However, a great need still exists for convenient and accurate point-of-care devices that can serve as a non-invasive diagnostic tool. In addition, there is an urgent need to decipher the scientific rationale and mechanisms that convey systemic diseases to saliva. Another promising technology called liquid biopsy enables detection of circulating tumor cells (CTCs) and fragments of tumor DNA in saliva, thus enabling non-invasive early detection of various cancers. The newly developed technology-electric field-induced release and measurement (EFIRM) provides near perfect detection of actionable mutations in lung cancer patients. These recent advances widened the salivary diagnostic approach from the oral cavity to the whole physiological system, and thus point towards a promising future of salivary diagnostics for personalized individual medicine applications including clinical decisions and post-treatment outcome predictions. Impact statement The purpose of this mini-review is to make an update about the present and future applications of saliva as a diagnostic biofluid in many fields of science such as dentistry, medicine and pharmacotherapy. Using saliva as a fluid for diagnostic purposes would be a huge breakthrough for both patients and healthcare providers since saliva collection is easy, non-invasive and inexpensive. We will go through the current main diagnostic applications of saliva, and provide a highlight on the emerging, newly developing technologies and tools for cancer screening, detection and monitoring.
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Acute declines in kidney #function occur in approximately 20%-30% of patients with acute decompensated heart failure, but its significance is unclear, and the importance of its context is not known.
In a study by McCallum et al., a decline in estimated glomerular filtration rate (eGFR), related to worsening kidney function, was not significantly associated with death and rehospitalization of the patient. However, there is a remarkable interaction between decline in eGFR and change in NT-proBNP. When both eGFR and NT-proBNP declined, acute decompensated heart failure patients had significantly better outcomes.
This suggests that including of congestion biomarkers may aid clinical interpretation of eGFR declines.
https://www.sciencedirect.com/science/article/pii/S0002934319305297#.
Why NT-proBNP ELISA from Biomedica?
√ FLEXIBLE and independent solution – can be run in every lab
√ SPECIFIC for NT-proBNP (1-76)
√ RELIABLE and REPRODUCIBLE results
√ GOOD CORRELATION with existing methods
https://www.bmgrp.com/product/cardiovascular/nt-probnp-elisa-biomedica/
Biomedica’s NT-proBNP ELISA complies with strict quality standards confirmed by RfB, an accredited international provider for proficiency testing for NT-proBNP. The Biomedica NT-proBNP ELISA successfully passes QC circle.
NT-proBNP ELISA successfully passes QC circle
– Link to RfB NT-proBNP Biomedica Certificate Proficiency Testing
-Link to RfB NT-proBNP Comments and Evaluation
FEATURES & BENEFITS
Biomedica NT-proBNP ELISA, cat# SK-1204:
- EASY – can be used in every lab
- RELIABLE – proved by RfB proficiency testing
- ROBUST & fully VALIDATED
- CE registered – for IVD use in EU
- GOOD ANALYTE STABILITY in serum and plasma
RELATED PUBLICATIONS
NT-proBNP as a Cornerstone for Prognosis in Valve Disease: All We Need Is Blood. Bergler-Klein J. J Am Coll Cardiol. 2020 Apr 14;75(14):1673-1675. doi: 10.1016/j.jacc.2020.02.030. PMID: 32273032.
NT-proBNP (N-Terminal Pro-B-Type Natriuretic Peptide) and the Risk of Stroke. Di Castelnuovo A, Veronesi G, Costanzo S, Zeller T, Schnabel RB, de Curtis A, Salomaa V, Borchini R, Ferrario M, Giampaoli S, Kee F, Söderberg S, Niiranen T, Kuulasmaa K, de Gaetano G, Donati MB, Blankenberg S, Iacoviello L; BiomarCaRE Investigators. Stroke. 2019 Mar;50(3):610-617. doi: 10.1161/STROKEAHA.118.023218. PMID: 30786848.
Abstract
Background and Purpose- NT-proBNP (N-terminal pro-B-type natriuretic peptide) is a risk factor for atrial fibrillation and a marker of cardiac function used in the detection of heart failure. Given the link between cardiac dysfunction and stroke, NT-proBNP is a candidate marker of stroke risk. Our aim was to evaluate the association of NT-proBNP with stroke and to determine the predictive value beyond a panel of established risk factors. Methods- Based on the Biomarkers for Cardiovascular Risk Assessment in Europe-Consortium, we analyzed data of 58 173 participants (50% men; mean age 52 y) free of stroke from 6 community-based cohorts. NT-proBNP measurements were performed in the central Biomarkers for Cardiovascular Risk Assessment in Europe laboratory. The outcomes considered were total stroke and subtypes of stroke (ischemic/hemorrhagic). Results- During a median follow-up time of 7.9 years, we observed 1550 stroke events (1176 ischemic). Increasing quarters of the NT-proBNP distribution were associated with increasing risk of stroke ( P for trend <0.0001; multivariable Cox regression analysis adjusted for risk factors and cardiac diseases). Individuals in the highest NT-proBNP quarter (NT-proBNP >82.2 pg/mL) had 2-fold (95% CI, 75%-151%) greater risk of stroke than individuals in the lowest quarter (NT-proBNP <20.4 pg/mL). The association remained unchanged when adjusted for interim coronary events during follow-up, and though it was somewhat heterogeneous across cohorts, it was highly homogenous according to cardiovascular risk profile or subtypes of stroke. The addition of NT-proBNP to a reference model increased the C-index discrimination measure by 0.006 ( P=0.0005), yielded a categorical net reclassification improvement of 2.0% in events and 1.4% in nonevents and an integrated discrimination improvement of 0.007. Conclusions- In European individuals free of stroke, levels of NT-proBNP are positively associated with risk of ischemic and hemorrhagic stroke, independently from several other risk factors and conditions. The addition of NT-proBNP to variables of established risk scores improves prediction of stroke, with a medium effect size.
NT-proBNP ELISA highlights:
Atrial fibrillation (AF) is the most common sustained arrhythmia, with an estimated 1 in 4 adults expected to develop it during their lifetime. Natriuretic peptide (NP) levels, including NT-proBNP and NT-proANP, are associated with several cardiovascular conditions, including coronary heart disease, heart failure, and hypertension (1, 2). They have also been linked to atrial fibrillation (AF) and cardiovascular risk in patients with AF. NPs vary in their sensitivity to different phenotypes of AF progression, while NT-proANP appears to be a specific biomarker of AF progression (1).
NT-proANP a biomarker in patients with persistent atrial fibrillation
In a recent study, researchers used mass spectrometric proteome profiling to investigate molecular differences between the right and left atria in patients with persistent AF. The analysis revealed that persistent AF is associated with a marked homogenization of right and left atrial proteomes; molecular differences that typically distinguish the two atria appear to diminish as AF progresses (3). This finding provides new insight into the atrial remodeling that occurs in persistent AF and highlights the value of advanced proteomics for understanding disease mechanisms at the tissue level.
The Biomedica NT-proANP ELISA was used in this study to quantify plasma NT-proANP in patients with persistent atrial fibrillation. NT-proANP is an important cardiac biomarker linked to atrial function and volume regulation.
Key findings:
- NT-proANP was significantly up-regulated in plasma samples from patients with persistent AF.
- While the left atrium is the traditional therapeutic target, atrial remodeling affects both the left and right atrium, suggesting the right atrium may deserve greater attention in clinical management.
Biomedica NT-proANP ELISA assay (cat. no. BI-20892)
-Trusted – widely cited in over 190 publications
-Quality – fully validated following international quality guidelines
-Convenient – kit includs pre-diluted calibrators and 2 controls
-Small sample volume – 10 µl / well
-Assay also suitable for rat and mouse samples – NT-proANP as a cardiovascular safety biomarker in rats Citations
Related products
NT-proBNP ELISA (cat. no. SK-1204)
BNP Fragment IA (cat. no. BI-20852W)
Rat NT-proBNP ELISA (cat. no. BI-1204R)
Literature
1. Role of NT-proANP and NT-proBNP in patients with atrial fibrillation: Association with atrial fibrillation progression phenotypes. Büttner P, Schumacher K, Dinov B, Zeynalova S, Sommer P, Bollmann A, Husser D, Hindricks G, Kornej J.Heart Rhythm. 2018 Aug;15(8):1132-1137. doi: 10.1016/j.hrthm.2018.03.021. Epub 2018 Mar 29. PMID: 29604419.
2. Natriuretic Peptide system and cardiovascular disease. Heart Views. Federico C. 2010 Mar;11(1):10-5. PMID: 21042458; PMCID: PMC2964706.
3. Mass spectrometric proteome profiling using a deep spectral library reveals homogenization of right and left atrial proteomes in persistent atrial fibrillation patients. Liutkute A, Berrandou TE, Kestel S, Schnelle M, Dschun O, Amedei HA, Neuenroth L, Rytkin E, Kyshynska O, Kensah G, El-Essawi A, Jebran AF, Danner BC, Baraki H, Kutschka I, Bremmer F, Urlaub H, Schmidt C, Bouatia-Naji N, Efimov IR, Brundel BJJM, Lenz C, Voigt N. Cardiovasc Res. 2026 Jun 5;122(8):1037-1054. doi: 10.1093/cvr/cvag076. PMID: 41928451; PMCID: PMC13261532.
With more than 40 years of expertise in developing and manufacturing high-quality ELISA kits, we support scientists and healthcare professionals with reliable tests that drive discovery and help translate research into diagnostics.
All kits are developed and manufactured by Biomedica Immunoassays — Austrian quality you can trust.
Explore Our Biomarker ELISA Assays
Explore our trusted and widely cited ELISA assays for biomarkers in bone metabolism, cardiovascular and renal diseases, cancer, and oxidative stress.
Biomedica ELISA Kits: Features & Benefits
-Easy to use: Ready-to-use calibrators and controls included, with color-coded reagents
-Comprehensive validation package: Assays optimized for clinical samples in accordance with high-level international quality standards
-Guaranteed high quality: Reliable results you can trust
-Widely cited: Referenced in more than 2,500 publications
Biomedica provides high-quality ELISA kits for key bone biomarkers
Explore Our Biomarker ELISA Assays
BONE & MINERAL METABOLISM
Biomedica provides high-quality ELISA kits for key bone biomarkers
SCLEROSTIN ELISA – SOST (cat. no. BI-20492)
OPG ELISA – Osteoprotegerin (cat. no. BI-20403)
RANKL ELISA–– soluble RANKL (cat. no. BI-20462)
DKK-1 ELISA – Dickkopf-1 (cat. no. BI-20413)
FGF23 intact ELISA – Fibroblast Growth Factor-23 intact (cat. no. BI-20700)
FGF23 C-terminal ELISA – Fibroblast Growth Factor-23 C-terminal (cat. no. BI-20702)
PERIOSTIN ELISA – POSTN (cat. no. BI-20433)
related citations:
- Sclerostin ELISA (BI-20492) and DKK-1 ELISA (BI-20413): Sclerostin and DKK1 circulating levels associate with low bone turnover in patients with chronic kidney disease Stages 3 and 4.
- FGF23 C-terminal (BI-20702) and FGF intact ELISA (BI-20700): C-terminal and intact FGF23 in kidney transplant recipients and their associations with overall graft survival.
CARDIOVASCULAR
NT-proBNP ELISA (cat.no. SK-1204)
rat NT-proBNP ELISA (cat.no. BI-1204R)
NT-proANP, ELISA human, rodent (cat.no. BI-20892)
NT-proCNP ELISA (cat.no. BI-20812)
Big Endothelin-1 ELISA (cat. no. BI-20082H)
Endostatin ELISA (cat. no. BI-20742)
Leucine-rich alpha-2-glycoprotein (LRG) ELISA (cat. no. BI-LRG)
related citations:
- Big Endothelin-1 ELISA (cat. no. BI-20082H) : Prognostic Value of Plasma Big Endothelin-1 in Patients Hospitalized for Heart Failure.
- NT-proBNP ELISA (cat.no. SK-1204): Intravenous mesenchymal stem cell transplantation mitigates pulmonary vascular remodeling but poses dose related risks in a pulmonary veno-occlusive disease model
- NT-proANP ELISA : Acute and Short‐Term Hemodynamic and Echocardiography Changes During and After Left Atrial Appendage Closure
- NT-proCNP ELISA (cat.no. BI-20812) : C-Type Natriuretic Peptide Preserves Vascular and Cardiac Function in Sepsis
KIDNEY & TRANSPLANT
Vanin-1 (urine) ELISA (cat. no. BI-VAN1U)
FGF23 intact ELISA – Fibroblast Growth Factor-23 intact (cat. no. BI-20700)
FGF23 C-terminal ELISA – Fibroblast Growth Factor-23 C-terminal (cat. no. BI-20702)
Human IL-6 ELISA Kit (cat. no. BI-IL6)
Human Endostatin ELISA (cat. no. BI-20742)
Anti-C4d Antibody (cat. no. BI-RC4D)
related citations:
- Human Vanin-1 (urine) ELISA (cat. no. BI-VAN1U): Urinary vanin-1 as a novel biomarker for survival in peripheral artery disease
- Vanin-1 ELISA (BI-VAN1U) and PERIOSTIN ELISA POSTN (cat. no. BI-20433): The Usefulness of Vanin-1 and Periostin as Markers of an Active Autoimmune Process or Renal Fibrosis in Children with IgA Nephropathy and IgA Vasculitis with Nephritis-A Pilot Study
- Anti-C4d Antibody (cat. no. BI-RC4D): Thirty-year follow-up of immunosuppression modulation: Impact on graft fibrosis and anti-HLA antibodies after pediatric liver transplantation
ONCOLOGY
FREE soluble RANKL HS ELISA | BI-20462
Human Periostin ELISA | BI-20433
Human DKK1 ELISA Kit | BI-20413
Leucine-rich alpha-2-glycoprotein (LRG1) ELISA | BI-LRG
related citations:
- LRG-1 ELISA (BI-LRG): High serum levels of leucine-rich α-2 glycoprotein 1 (LRG-1) are associated with poor survival in patients with early breast cancer.
- FREE soluble RANKL HS ELISA | BI-20462: Retrospective Evaluation of Bone Turnover Markers in Serum for the Prediction of Metastases Development in Breast Cancer Patients: A Cohort Study
OXIDATIVE STRESS
oLAB (Anti-Oxidized LDL Autoantibodies) ELISA | BI-20032
OxyStat Assay – detection of biological peroxides | BI-5007
related citations:
- oxLDL – oLAB ELISA (BI-20032): Overview of Clinical Relevance of Antibodies Against Oxidized Low-Density Lipoprotein (oLAb) Within Three Decades by ELISA Technology
- OxyStat Assay – The role of seminal reactive oxygen species assessment in the setting of infertility and early pregnancy loss
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With more than 40 years of experience, we specialize in the development and manufacture of high-quality ELISA assay kits for clinical research biomarkers.
Explore our ELISA assay product brochure.
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About us
BIOMEDICA Immunoassays develops and manufactures high-quality, widely cited immunoassays for clinical and pre-clinical applications in bone and cardiorenal diseases. For selected biomarkers, BIOMEDICA has become a global leader, including Sclerostin, free sRANKL, OPG, and NT-proCNP.
All BIOMEDICA ELISA assays are fully validated according to international quality guidelines. The assays include ready-to-use serum-based calibrators and controls, helping researchers generate biologically reliable data.
Features & Benefits of BIOMEDICA ELISA Assay Kits
Trusted – cited in more than 2,500 publications
Highly specific – developed with well-characterized, epitope-mapped antibodies
Fully validated – comprehensive validation according to international quality guidelines
Convenient – ready-to-use, color-coded reagents with controls included
Biomarker ELISA Assays for Bone-Mineral Metabolism & Cardio-Renal Diseases
–Intact FGF23 ELISA Kit | BI-20700
–FGF23 (C-terminal) multi-matrix ELISA Kit | BI-20702
–FREE soluble RANKL HS ELISA | BI-20462
–OPG ELISA Kit (Human Osteoprotegerin) | BI-20403
–Rat NT-proBNP ELISA | BI-1204R
Selected citations
Profiling bone status indices reveals evidence of a low-turnover bone phenotype in type 2 diabetes: findings from the DiaFALL cohort. Rasmussen, Kvist, Bech, Lykkeboe, Starup-Linde, Handberg, van den Bergh, Vestergaard; Osteoporos Int (2026) .
Endocrine Functions of Bone Are Suppressed by Orally Administered Glucose Regardless of Bodyweight. Jalava, Heino, Nuutila, Virtanen, Ivaska; Clin Endocrinol (Oxf) (2026) 104 (2), 130-138 .
Plasma C-Type Natriuretic Peptide: Emerging Applications in Disorders of Skeletal Growth. Espiner, E., Prickett, T., Olney, R., 2018. Horm Res Paediatr 90, 345–357.
Subclinically low BMD in young men is associated with compromised bone microarchitecture and lower lean mass. Goulart, Kargl, Sterczala, Sekel, Wunderlich, Mroz, Lovalekar, Martin, Fazeli, Cauley, O’Leary, Greeves, Koltun, Nindl. J Endocr Soc (2026) 10 (3), bvag003.
ELISA (enzyme-linked immunosorbent assay) is one of the most widely used methods for quantifying analytes in biological samples. In addition to its high sensitivity and specificity, ELISA is valued for its relative simplicity and cost-effectiveness compared with many other analytical techniques. However, while the procedure may appear straightforward, accurate measurement of biological samples can involve important technical considerations.
How to Achieve Reliable and Reproducible ELISA Results
Concept of a Sandwich ELISA Assay
In a typical sandwich ELISA, a 96-well microtiter plate is pre-coated with a target-specific capture antibody, which may be monoclonal or polyclonal. The sample is then added to the wells and incubated, allowing the protein of interest to bind to the immobilized capture antibody.
Next, a detection antibody is added. This antibody binds to a separate site on the target antigen, forming an antibody–antigen–antibody complex: capture antibody–target antigen–detection antibody.
ELISA Assay Principle
Quantification of the results is achieved by introducing an enzyme-conjugated antibody that binds specifically to the detection antibody, catalyzing a colorimetric enzymatic reaction. After a brief incubation with an appropriate substrate, the amount of enzyme conjugate bound in the well can be detected. The resulting color change in the well is then measurable using a standard microtiter plate ELISA reader, which records the absorbance (optical density). A higher signal indicates a higher concentration of the analyte in the sample, corresponding to the range established by the standard curve.
Example of an ELISA Standard Curve
How to Achieve Reliable and Reproducible ELISA Results
To obtain reliable results it is recommended to choose an ELISA Assay that has gone through a full validation protocol. Results (validation data) must be provided that include data on specificity, sensitivity (LOD, LLOQ), accuracy/recovery, parallelism and dilution linearity, precision (within-run and in-between run), calibration, stability, and lot-to-lot consistency.
ELISA Assay – microtiter plate
How to Achieve Reliable and Reproducible ELISA Results
Key Elements of ELISA Assay Validation
1. Specificity
Specificity ensures accurate measurement of the target protein or biomarker.The performance of an ELISA assay depends largely on the quality of the antibody pair used to detect the analyte of interest.
To achieve high specificity, the assay developer should:
-Select antibody pairs with high affinity and specificity, ideally with well-characterized binding sites.
-Optimize the ELISA kit to accurately quantify biomarkers in both healthy and disease-state samples.
2. Sensitivity
Sensitivity describes an ELISA assay’s ability to detect very low concentrations of the target analyte.
In an ELISA, sensitivity is determined by the lowest amount of protein that can be detected using the antibody pair included in the kit. It depends largely on the affinity of the solid-phase, or coating, antibody. Using a higher-affinity antibody can therefore improve assay sensitivity.
-Analytical sensitivity / Limit of Detection (LOD): The lowest analyte concentration that can be detected with statistical significance using a specific analytical method. It is typically calculated as the background signal plus or minus two standard deviations.
-Functional sensitivity / Lower Limit of Quantification (LLOQ): The lowest analyte concentration that can be reliably detected and quantified.
3. Accuracy / Recovery
Accuracy evaluates whether an ELISA assay correctly detects the presence or absence of the target protein or antigen in different sample matrices, such as serum and plasma. It also helps identify potential matrix effects that could interfere with accurate measurement of the analyte.
Ideally, accuracy should be assessed in every sample type in which the analyte will be measured, including serum, EDTA plasma, and heparin plasma. To evaluate recovery, each matrix is spiked with known concentrations of recombinant analyte. The samples are then measured against the assay’s standard curve, and the observed concentrations are compared with the expected, or nominal, values.
4. Parallelism / Dilution Linearity
Parallelism and dilution linearity confirm that samples can be measured accurately and reliably across different dilution levels.
-Parallelism assesses whether samples containing high endogenous concentrations of the analyte produce results that remain consistent with the assay’s standard curve after serial dilution. This evaluation can reveal differences in antibody binding affinity between the endogenous analyte in real samples and the recombinant analyte used to calibrate the ELISA. Parallelism should always be evaluated during assay validation using samples with naturally occurring analyte levels.
-Dilution linearity evaluates analyte recovery in samples spiked with the recombinant analyte used to generate the assay standards. It determines whether measured concentrations remain proportional and accurate following serial dilution.
5. Precision
Precision assesses an ELISA assay’s ability to produce consistent and reliable results both within a single run and across different kit lots.
-Within-run precision (repeatability): Evaluates variation among multiple measurements of the same sample performed during a single assay run.
-Between-run precision: Evaluates the consistency of results when samples are tested repeatedly in separate assay runs, including runs performed with different ELISA kit lots. This confirms that the assay provides accurate and reproducible results over time and across lot-to-lot variations.
6. Calibration
Calibration enables accurate quantification of the target protein.
-Accurate measurement depends on the linearity and reproducibility of the assay’s standard curve. During ELISA kit optimization, variability among calibrator results should be minimized. When available, standards traceable to NIBSC or WHO reference materials should be used to support harmonized assay standardization.
7. Stability
Stability evaluates both the integrity of the target analyte in sample matrices and the stability of ELISA kit reagents.
During assay development, all assay components should be assessed for stability, along with the analyte in relevant sample types, such as serum and plasma.
-Analyte stability: This can be evaluated by exposing samples to repeated freeze–thaw cycles or storing them at room temperature for a defined period before analysis.
-Kit reagent stability: ELISA reagents should be tested under different temperature conditions for specified time periods to confirm their stability.
-Shelf-life: Real-time stability testing should be performed throughout the intended shelf-life of the kit. For example, reagents stored at 4°C may be evaluated after 6, 12, and 18 months.
8. Lot-to-Lot Consistency
Lot-to-lot consistency ensures that different ELISA kit batches provide comparable and reliable results.
-To assess consistency, each kit lot is tested using in-house control samples, including serum and plasma samples containing endogenous analyte as well as samples spiked with recombinant analyte. Results are evaluated to confirm that they fall within established quality-control ranges.
Discover our Biomarker ELISA Kit Collection
Achieving Reproducible ELISA Assay Results
BIOMEDICA ELISA kits undergo comprehensive validation in accordance with international quality guidelines. This helps ensure that your valuable samples are measured accurately and that the assay specifically detects the analyte of interest.
Learn more about achieving reproducible ELISA assay results on our website : QUALITY
Why Choose BIOMEDICA ELISA Kits?
-Specific: Accurate biomarker detection using well-characterized antibodies.
-Reliable: Validated using clinical samples.
-Reproducible: Consistent performance across ELISA kit lots.
Biomedica- High Quality Guaranteed
Further reading
A Practical Guide to Immunoassay Method Validation.
Andreasson U, Perret-Liaudet A, van Waalwijk van Doorn LJ, Blennow K, Chiasserini D, Engelborghs S, Fladby T, Genc S, Kruse N, Kuiperij HB, Kulic L, Lewczuk P, Mollenhauer B, Mroczko B, Parnetti L, Vanmechelen E, Verbeek MM, Winblad B, Zetterberg H, Koel-Simmelink M, Teunissen CE.Front Neurol. 2015 Aug 19;6:179. doi: 10.3389/fneur.2015.00179. PMID: 26347708; PMCID: PMC4541289.
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Big ET-1 is a promising cardiotoxicity marker in childhood cancer survivors
Advancements in oncological therapies have resulted in a childhood cancer survivor (CCS) long-term survival rate exceeding 80%. However, up to 60% of CCS are exposed to cardiotoxic treatments, significantly increasing their risk of congestive heart failure (CHF). CHF is a leading cause of long-term morbidity and mortality, with CCS facing a 15-fold higher incidence of CHF and a 7-fold greater risk of premature cardiac death compared to the general population (1).
Big Endothelin-1 (Big ET-1) is the inactive precursor of Endothelin-1 (ET-1), a 21-amino acid peptide that functions as one of the most potent vasoconstrictors in the human cardiovascular system. Under physiological conditions, Big ET-1 is cleaved by endothelin-converting enzyme (ECE) to generate active ET-1, which exerts its effects primarily through endothelin receptor type A (ETA) and type B (ETB) on vascular smooth muscle cells and endothelial cells (2).
Endothelial damage is characterized by dysfunction of the vascular endothelium, leading to increased permeability, pro-inflammatory and pro-thrombotic states, and impaired vasodilatory responses (3). Elevated circulating levels of Big ET-1 serve as a biomarker for endothelial cell activation and injury because increased production or impaired processing of Big ET-1 reflects endothelial cell distress (4). This dysfunction is a central mechanism in the pathogenesis of various cardiovascular diseases, including hypertension, atherosclerosis, and cardiomyopathy.
Big ET-1 is a promising cardiotoxicity marker in childhood cancer survivors
A recent study published in Cardiovascular Toxicology, investigated the long-term cardiotoxic effects of cancer therapy in CCS through a dual approach combining CMR imaging and blood biomarkers (5).
Big Endothelin-1 was measured in blood samples with an ELISA assay from BIOMEDICA.
Big-ET-1 ELISA kit highlights (BI-20082H)
– HIGH SENSITIVITY – direct measurement
– RELIABLE – Fully validated according to international guidelines
– Published cut-off values
– TRUSTED – widely cited in over 90 publications
Biomedica ELISA Assay kit box and reagent set
Big ET-1 is a stable marker for investigating endothelial damage in cardiovascular diseases.
Key Findings
- CMR imaging revealed differences between CCS and control subjects
- In CCS, biomarkers indicating endothelial activation (Big ET-1) and oxidative stress (MPO, IMA) were elevated
- Blood biomarkers can enhance early detection and risk assessment of myocardial abnormalities
Monitoring Big ET-1 alongside imaging may improve long-term cardiac outcomes in childhood cancer survivors.
Long-term Subclinical Cardiotoxicity of Modern Cardiotoxic Treatment Protocols in Childhood Cancer Survivors Assessed by Cardiovascular Magnetic Resonance T1 Mapping and Circulatory Biomarkers. Panovský R, Tomandlová M, Mojica-Pisciotti ML, Kepák T, Máchal J, Feitová V, Frič J, Hortová-Kohoutková M, Holeček T, Tomandl J, Opatřil L, Kincl V.Cardiovasc Toxicol. 2026 Jan 28;26(2):23. doi: 10.1007/s12012-026-10098-8. PMID: 41604073; PMCID: PMC12852242.
Abstract
Childhood cancer survivors (CCS) are at increased risk of developing heart disease due to the cardiotoxic effects of oncological treatment. This study aimed to investigate the long-term cardiotoxic effects of cancer therapy in CCS using a multimodal approach combining cardiac magnetic resonance (CMR) imaging and circulating blood biomarkers. A total of 117 CCS (mean age 24.7 ± 5.2 years), at least five years post-treatment and in complete remission, were prospectively enrolled. All participants underwent CMR, including T1 mapping, and blood analysis for biomarkers of endothelial damage and oxidative stress. Parameters were compared with sex- and age-matched healthy control groups. Anthracycline treatment was administered in 82.9% of CCS (mean cumulative doxorubicin equivalent dose 231.7 ± 92.0 mg/m²). Left ventricular ejection fraction and mitral annular plane systolic excursion were significantly reduced in CCS compared to controls (59.0 ± 5.5% vs. 67.2 ± 6.9%, p < 0.001; 12.5 ± 1.7 mm vs. 13.9 ± 2.2 mm, p = 0.001). Late gadolinium enhancement was detected in four CCS. No significant differences in global native T1 relaxation time or extracellular volume were observed. N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels remained within normal limits but correlated with native T1, ECV, and MAPSE. Levels of myeloperoxidase, big endothelin-1, and ischemia-modified albumin were significantly higher than in controls. Subclinical myocardial changes were detected in long-term CCS using CMR and circulating biomarkers. These findings support the utility of a multimodal approach for the early identification of individuals at increased cardiovascular risk after childhood cancer treatment.
Literature
- Long-term Subclinical Cardiotoxicity of Modern Cardiotoxic Treatment Protocols in Childhood Cancer Survivors Assessed by Cardiovascular Magnetic Resonance T1 Mapping and Circulatory Biomarkers. Panovský R, Tomandlová M, Mojica-Pisciotti ML, Kepák T, Máchal J, Feitová V, Frič J, Hortová-Kohoutková M, Holeček T, Tomandl J, Opatřil L, Kincl V.Cardiovasc Toxicol. 2026 Jan 28;26(2):23. doi: 10.1007/s12012-026-10098-8. PMID: 41604073; PMCID: PMC12852242.
- Endothelin and the Cardiovascular System: The Long Journey and Where We Are Going. Haryono A, Ramadhiani R, Ryanto GRT, Emoto N. Biology (Basel). 2022 May 16;11(5):759. doi: 10.3390/biology11050759. PMID: 35625487; PMCID: PMC9138590.
- Endothelial Dysfunction, Inflammation and Coronary Artery Disease: Potential Biomarkers and Promising Therapeutical Approaches. Medina-Leyte DJ, Zepeda-García O, Domínguez-Pérez M, González-Garrido A, Villarreal-Molina T, Jacobo-Albavera L. Int J Mol Sci. 2021 Apr 8;22(8):3850. doi: 10.3390/ijms22083850. PMID: 33917744; PMCID: PMC8068178.
- Plasma big endothelin-1 levels at admission and future cardiovascular outcomes: A cohort study in patients with stable coronary artery disease. Zhou BY, Guo YL, Wu NQ, Zhu CG, Gao Y, Qing P, Li XL, Wang Y, Dong Q, Liu G, Xu RX, Cui CJ, Sun J, Li JJ. Int J Cardiol. 2017 Mar 1;230:76-79. doi: 10.1016/j.ijcard.2016.12.082. Epub 2016 Dec 21. PMID: 28038820.
- Long-term Subclinical Cardiotoxicity of Modern Cardiotoxic Treatment Protocols in Childhood Cancer Survivors Assessed by Cardiovascular Magnetic Resonance T1 Mapping and Circulatory Biomarkers. Panovský R, Tomandlová M, Mojica-Pisciotti ML, Kepák T, Máchal J, Feitová V, Frič J, Hortová-Kohoutková M, Holeček T, Tomandl J, Opatřil L, Kincl V. Cardiovasc Toxicol. 2026 Jan 28;26(2):23. doi: 10.1007/s12012-026-10098-8. PMID: 41604073; PMCID: PMC12852242.
Approximately 1 in 10 people are affected by chronic kidney disease (CKD), impacting over 800 million individuals globally (1-3). CKD is a progressive condition where the kidneys gradually lose their ability to function properly.
Early intervention is essential to preserving kidney health, slowing the progression of kidney disease and its complications, decreasing the risk of risk of cardiovascular disease, and preventing early death related to kidney and cardiovascular conditions (4).
World Kidney Day – March 12, 2026
What are the contributing factors to CKD?
Age over 60, diabetes, high blood pressure, heart disease, obesity, and certain medications are some of the known risk factors for kidney disease.
How can we maintain healthy kidneys?
Good nutrition, regular exercise, and adequate fluid intake are some of the ways to support kidney health.
Are your kidneys healthy? Take the quiz
BIOMEDICA´s Biomarker ELISA Kits in Clinical Nephrology
- FGF23 (C-terminal) |BI-20700 and FGF23 intact ELISA |BI-20700
- Vanin-1 (urine) ELISA | BI-VAN1U
- Endostatin ELISA | BI-20742
- Periostin ELISA | BI-20422
- Sclerostin ELISA |BI-20492 and Bioactive Sclerostin ELISA |BI-20472
Related Products:
Osteoprotegerin ELISA, NT-proBNP ELISA, Anti-C4d Antibody
Why laboratories choose BIOMEDICA ELISA kits
- ROBUST & RELIABLE ASSAYS
- Widely cited in over 1700 peer-reviewed publications
- Validated according to international guidelines
- High specificity, enabling reliable biomarker measurement in healthy individuals
Are you planning a clinical study ELISA kits for clinical research in kidney disease
Biomarkers in Clinical Nephrology – check out our broshure
More information on kidney health can be found on the following websites:
- ISN, World Kidney Day 2026 – International Society of Nephrology
- Are your kidneys healthy- Quiz – 20 years World Kidney Day
- Detect early, protect kidney health: World Kidney Day 2025. Waith FM, Bresolin NL, Antwi S. Pediatr Nephrol. 2025 May;40(5):1511-1514. doi: 10.1007/s00467-025-06714-4. Epub 2025 Feb 17. PMID: 39960639. For full publication- click here
- Are your kidneys ok? Detect early to protect kidney health. Vassalotti JA, Francis A, Soares Dos Santos AC Jr, Correa-Rotter R, Abdellatif D, Hsiao LL, Roumeliotis S, Haris A, Kumaraswami LA, Lui SF, Balducci A, Liakopoulos V; World Kidney Day Joint Steering Committee. Ren Fail. 2025 Dec;47(1):2503514. PMID: 40394853
Abstract
Early identification of kidney disease can protect kidney health, prevent kidney disease progression and related complications, reduce cardiovascular disease risk and decrease mortality. We must ask “Are your kidneys ok?” using serum creatinine to estimate kidney function and urine albumin to assess for kidney and endothelial damage. Evaluation for causes and risk factors for chronic kidney disease (CKD) includes testing for diabetes and measurement of blood pressure and body mass index. This World Kidney Day we assert that case-finding in high-risk populations, or even population level screening, can decrease the burden of kidney disease globally. Early-stage CKD is asymptomatic, simple to test for and recent paradigm shifting CKD treatments such as sodium glucose co-transporter-2 inhibitors dramatically improve outcomes and favor the cost-benefit analysis for screening or case-finding programs. Despite this, numerous barriers exist, including resource allocation, healthcare funding, healthcare infrastructure and healthcare-professional and population awareness of kidney disease. Coordinated efforts by major kidney non-governmental organizations to prioritize the kidney health agenda for governments and aligning early detection efforts with other current programs will maximize efficiencies.
Additonal publications:
IPNA’s commitment to world kidney day 2026: caring for little kidneys and protecting the planet. Shroff R, Sivaram P, Tarter A, Phiri EM, Antwi S, Ocheke I, Penido MG, Mccarthy F, Lou-Meda R, Adalat S, He G, Kermond R, Bayazit AK, Raina R; IPNA Green Nephrology Taskforce, IPNA Special Projects Committee. Pediatr Nephrol. 2026 Feb 24. PMID: 41733668.
Big Endothelin-1 (Big ET-1) is the precursor to the most potent vasoconstrictor peptide Endothelin-1 (ET-1), which is mainly produced by endothelial cells (1). Interestingly, there is evidence of stimulated ET-1 release from various immune cells, including macrophages and dendritic cells, indicating that these cells can also synthesize ET-1 (2).
While ET-1 is essential in regulating vascular tone and blood pressure, Big ET-1 itself is biologically inactive and mainly functions as a reservoir for ET-1. Big ET-1 has a longer half-life compared to ET-1 and circulates in equal molar amounts, making it a more stable and reliable biomarker (3). Elevated levels of Big ET-1 can signal vascular dysfunction and are linked to cardiovascular conditions such as hypertension and heart failure (4).
Prognostic value of Big Endothelin-1 in heart failure
A study recently explored the prognostic value of Big ET-1 in 4,368 patients hospitalized with heart failure with a median follow-up of 875 days (5).
Key findings:
- Elevated Big ET-1 was independently associated with cardiovascular death in patients with HF.
- Big ET-1 is a promising indicator of HF prognosis.
Big Endothelin-1 and NT-proBNP were measured with the following ELISA assay kits:
Big Endothelin-1 ELISA | BI-20082H
- Direct measurement – 50µl serum/plasma per well.
- High Quality – fully validated according to international quality guidelines
- Trusted – cited in over 90 publications
- Protocol booklet click here
- Convenient – ready -to-use reagents
- Flexible – can be run in every lab
- Two controls included
- High quality – fully validated according to international quality guidelines
- Trusted- cited in over 140 publications
- Protocol booklet click here
Discover our Biomarker ELISA Kit Collection
Literature
- Endothelin-1 in Health and Disease. Banecki KMRM, Dora KA. Int J Mol Sci. 2023 Jul 10;24(14):11295. doi: 10.3390/ijms241411295. PMID: 37511055; PMCID: PMC10379484.
- Endothelin-1 in Health and Disease. Banecki KMRM, Dora KA. Int J Mol Sci. 2023 Jul 10;24(14):11295. doi: 10.3390/ijms241411295. PMID: 37511055; PMCID: PMC10379484.
- Biomarkers in aortic dissection. Wen D, Zhou XL, Li JJ, Hui RT. Clin Chim Acta. 2011 Apr 11;412(9-10):688-95. doi: 10.1016/j.cca.2010.12.039. Epub 2011 Jan 13. PMID: 21237193.
- Plasma concentration of big endothelin-1 and its relation with plasma NT-proBNP and ventricular function in heart failure patients. Rivera M, Cortés R, Portolés M, Valero R, Sancho-Tello MJ, Martínez-Dolz L, Sevilla B, Taléns-Visconti R, Jordán A, Miró V, Pérez-Boscá JL, Marín F, Climent V, García de Burgos F, Payá R, Sogorb F, Bertomeu V, Salvador A. Rev Esp Cardiol. 2005 Mar;58(3):278-84. Spanish. PMID: 15766450.
- Prognostic Value of Plasma Big Endothelin-1 in Patients Hospitalized for Heart Failure. Wang J, Feng J, Tse G, Zhai M, Huang Y, Zhou Q, Zhuang X, Liu H, Zhang Y, Zhang J. Korean Circ J. 2025 Aug;55(8):705-717. doi: 10.4070/kcj.2024.0354. Epub 2025 Apr 11. PMID: 40345830; PMCID: PMC12314060.
Prognostic Value of Plasma Big Endothelin-1 in Patients Hospitalized for Heart Failure.
Abstract:
Background and objectives: Endothelin-1 (ET-1) is a potent vasoconstrictor and multifunctional neuroendocrine hormone that is closely associated with the pathophysiology of heart failure (HF). Currently, the evidence about the predictive value of big ET-1 in HF remains insufficient. This study aims to investigate the prognostic importance of big ET-1 in HF.
Methods: We examined the incidence of cardiovascular death in a single-center retrospective cohort of HF (de novo, worsening, or chronic included).
Results: The 4,368 hospitalized HF patients were enrolled. During the median follow-up of 875 (365-1,400) days, 851 (19.5%) patients had primary outcome events. Big ET-1 was independently associated with cardiovascular death as a continuous variable (hazard ratio [HR], 1.13; 95% confidence interval [CI], 1.06-1.21; p<0.001) and by tertiles (HR, 1.35; 95% CI, 1.06-1.72; p=0.017 for tertile 2 and HR, 1.70; 95% CI, 1.32-2.19; p<0.001 for tertile 3). This pattern of risk was maintained after further adjustment for NT-proBNP (HR, 1.11; 95% CI, 1.03-1.19; p=0.006 for continuous variable, HR, 1.30; 95% CI, 1.02-1.67; p=0.035 for tertile 2, and HR, 1.69; 95% CI, 1.23-2.05; p=0.034 for tertile 3). Net reclassification index (NRI) and integrated discrimination improvement (IDI) analysis showed that big ET-1 provided additional predictive power in combination with NT-proBNP (NRI, 0.11; 95% CI, 0.04-0.17; p=0.012 and IDI, 0.012; 95% CI, 0.003-0.017; p<0.001).
Conclusions: Elevated big ET-1 was independently associated with cardiovascular death in patients with HF. Big ET-1 may be a promising indicator of HF prognosis. In combination with NT-proBNP, big ET-1 may provide incremental predictive information.
February is designated as “Heart Month,” a time to raise awareness about cardiovascular health, promoting healthy lifestyles, and encouraging prevention of heart disease. It aims to educate the public on the risk factors, symptoms, and treatments associated with heart-related conditions, highlighting the importance of maintaining a healthy heart through proper nutrition, regular exercise, avoiding smoking, managing stress, and monitoring blood pressure and cholesterol levels (1-3).
HEART MONTH – focusing on heart health and prevention
Biomarkers in cardiovascular disease
Biomarkers can serve as biochemical indicators that offer crucial insights into disease prognosis and progression, and in predicting the response to treatments. Biomarkers are also utilized in clinical trials or applied in toxicology, including preclinical drug safety evaluations. Advances in biomarker research have transformed how heart conditions are diagnosed and managed (4).
Biomedica offers a wide range of ELISA kits for the accurate measurement of biomarkers related to heart and cardiovascular diseases including NT-proBNP, Big Endothelin-1, FGF23, and markers related to oxidative stress.
- NT-proBNP – human (cat. no. SK-1204)
- NT-proBNP- rat (cat. no. BI-1204R)
- NT-proANP – human, rodent (cat. no. BI-20892 )
- Big Endothelin-1 (cat. no. BI-20082H)
- FGF23 intact (cat. no. BI-20700)
- FGF23 c-terminal (cat. no. BI-20702)
- Endostatin
- Oxidized LDL (low density lipoprotein) antibodies, oLAB – (BI-20032)
- IL-6 (cat. no. BI-IL6)
NT-proBNP ∙ NT-proANP ∙ BigET-1 ∙ FGF23 ∙ Endostatin ∙ LRG1 ∙ oxLDL Antibodies ∙ IL-6
NT-proBNP (N-terminal pro b-type natriuretic peptide) is the inactive amino-terminal fragment cleaved from proBNP, a prohormone produced predominantly by ventricular myocytes in response to increased myocardial wall stress and volume overload. Due to its stability and longer half-life compared to active BNP, NT-proBNP serves as a sensitive and specific biomarker for the diagnosis of heart failure. NT-proBNP is commonly used in the diagnosis and management of heart failure, reflecting increased intracardiac pressures and ventricular dilation (5-7). It aids in differentiating cardiac from non-cardiac causes of dyspnea, stratifying disease severity, guiding therapeutic decisions, and predicting morbidity and mortality outcomes in heart failure patients (8).
NT-proANP (N-terminal pro-atrial natriuretic peptide) is a biomarker released by the heart in response to atrial stretching and elevated blood volume. It is utilized to evaluate heart failure and detect cardiac stress, helping in the diagnosis and management of various cardiovascular conditions (9).
Big Endothelin-1 (Big ET-1) is a vasoconstrictive peptide and the precursor to Endothelin-1 (ET-1), which is the biologically active form. Elevated levels of Big ET-1 serve as an independent marker of heart failure in cases of congestive heart disease (10). Due to its longer half-life compared to ET-1 and its presence in circulation in equimolar amounts with ET-1, Big ET-1 is considered a more reliable biomarker.
Fibroblast Growth Factor-23 (FGF23) is a hormone involved in regulating phosphate metabolism. It has emerged as a potential biomarker for cardiovascular risk, with elevated circulating FGF23 levels being linked to adverse outcomes such as heart failure and arrhythmias (11, 12).
Endostatin, a fragment derived from collagen XVIII, is an extracellular matrix protein that plays a crucial role in the development of chronic kidney and heart diseases. In this study by Yaghoubi A et al, Endostatin levels were found to be elevated in patients hospitalized with acute dyspnea who had a history of chronic heart failure (CHF), and these elevated levels were associated with increased mortality at 3 months. Additionally, endostatin was linked to both 1-month and 3-month mortality in patients presenting with acute dyspnea who had no previous history of CHF (13, 14).
Leucine-rich alpha-2-glycoprotein (LRG) is a secreted protein that plays a significant role in pathological ocular neovascularization. It is also implicated in various conditions such as cardiovascular disease, diabetes, inflammatory disorders, and cancer. Recent research has identified LRG as an independent predictor of diastolic dysfunction (DD), due to myocardial fibrosis (15).
Oxidized LDL (low density lipoprotein) antibodies, oLAB
Oxidized LDL (oxLDL) antibodies are directed against epitopes on oxidized low-density lipoprotein particles. OxLDL results from the oxidative modification of native LDL particles, involving lipid peroxidation and protein oxidation, which generate neoantigens recognized as foreign by the immune system (12). The production of anti-oxLDL antibodies, predominantly IgG and IgM subclasses, reflects ongoing oxidative stress and lipid peroxidation processes within atherosclerotic lesions. These antibodies can participate in immune complex formation, potentially influencing atherogenesis through pro-inflammatory or anti-inflammatory mechanisms. Elevated levels of anti-oxLDL antibodies have been correlated with the presence and progression of atherosclerotic plaques, making them valuable biomarkers for cardiovascular disease risk assessment. Their precise role in atherosclerosis pathophysiology remains complex, involving both protective clearance of modified lipoproteins and pro-inflammatory immune responses that may exacerbate vascular injury (16-18).
Interleukin-6 (IL-6)
IL-6 signaling plays a critical role in the inflammatory processes underlying cardiovascular disease (CVD). IL-6 is a cytokine that promotes inflammation, endothelial dysfunction, and plaque formation in atherosclerosis (15). It signals through its receptor complex, activating pathways such as JAK/STAT, which contribute to vascular inflammation and instability. Anti-IL-6 therapeutics, including monoclonal antibodies like tocilizumab, target this cytokine or its receptor to reduce inflammation. These agents have shown potential in lowering cardiovascular risk by modulating inflammatory responses, making IL-6 inhibition a promising strategy for managing CVD associated with chronic inflammation (19, 20).
Literature
- 2021 Dietary Guidance to Improve Cardiovascular Health: A Scientific Statement From the American Heart Association. Lichtenstein AH, Appel LJ, Vadiveloo M, Hu FB, Kris-Etherton PM, Rebholz CM, Sacks FM, Thorndike AN, Van Horn L, Wylie-Rosett J. Circulation. 2021 Dec 7;144(23):e472-e487. doi: 10.1161/CIR.0000000000001031. Epub 2021 Nov 2. PMID: 34724806.
- A Heart-Healthy Diet for Cardiovascular Disease Prevention: Where Are We Now? Diab A, Dastmalchi LN, Gulati M, Michos ED. Vasc Health Risk Manag. 2023 Apr 21;19:237-253. doi: 10.2147/VHRM.S379874. PMID: 37113563; PMCID: PMC10128075.
- Physical Activity Over the Lifecourse and Cardiovascular Disease. Perry AS, Dooley EE, Master H, Spartano NL, Brittain EL, Pettee Gabriel K. Circ Res. 2023 Jun 9;132(12):1725-1740. doi: 10.1161/CIRCRESAHA.123.322121. Epub 2023 Jun 8. PMID: 37289900; PMCID: PMC10254078.
- Advancements in Biomarkers for Early Detection and Risk Stratification of Cardiovascular Diseases-A Literature Review. Nazir A, Nazir A, Afzaal U, Aman S, Sadiq SUR, Akah OZ, Jamal MSW, Hassan SZ. Health Sci Rep. 2025 May 26;8(5):e70878. doi: 10.1002/hsr2.70878. PMID: 40432692; PMCID: PMC12106349.
- Natriuretic Peptides: Role in the Diagnosis and Management of Heart Failure: A Scientific Statement From the Heart Failure Association of the European Society of Cardiology, Heart Failure Society of America and Japanese Heart Failure Society. Tsutsui H, Albert NM, Coats AJS, Anker SD, Bayes-Genis A, Butler J, Chioncel O, Defilippi CR, Drazner MH, Felker GM, Filippatos G, Fiuzat M, Ide T, Januzzi JL Jr, Kinugawa K, Kuwahara K, Matsue Y, Mentz RJ, Metra M, Pandey A, Rosano G, Saito Y, Sakata Y, Sato N, Seferovic PM, Teerlink J, Yamamoto K, Yoshimura MJ Card Fail. 2023 May;29(5):787-804. doi: 10.1016/j.cardfail.2023.02.009. Epub 2023 Apr 17. PMID: 37117140.
- Practical algorithms for early diagnosis of heart failure and heart stress using NT-proBNP: A clinical consensus statement from the Heart Failure Association of the ESC. Bayes-Genis A, Docherty KF, Petrie MC, Januzzi JL, Mueller C, Anderson L, Bozkurt B, Butler J, Chioncel O, Cleland JGF, Christodorescu R, Del Prato S, Gustafsson F, Lam CSP, Moura B, Pop-Busui R, Seferovic P, Volterrani M, Vaduganathan M, Metra M, Rosano G. Eur J Heart Fail. 2023 Nov;25(11):1891-1898. doi: 10.1002/ejhf.3036. Epub 2023 Sep 26. PMID: 37712339.
- Essential biochemistry and physiology of (NT-pro)BNP. Hall C.Eur J Heart Fail. 2004;6:257–260. doi:10.1016/j.ejheart.2003.12.015.
- Comprehensive Review of Cardiovascular Disease Management: Cardiac Biomarkers, Imaging Modalities, Pharmacotherapy, Surgical Interventions, and Herbal Remedies. Netala VR, Teertam SK, Li H, Zhang Z. A Cells. 2024 Sep 1;13(17):1471. doi: 10.3390/cells13171471. PMID: 39273041; PMCID: PMC11394358.
- Prognostic value of NT-proANP levels on major cardiovascular outcomes in a 31-year follow-up study depends on baseline morbidity. Sakko S, Perkiömäki J, Ylitalo A, Huikuri H, Ukkola O, Koivunen P, Tapio J. Sci Rep. 2025 May 28;15(1):18660. doi: 10.1038/s41598-025-03819-6. PMID: 40436983; PMCID: PMC12119872.
- Elevated Plasma Big Endothelin-1 at Admission Is Associated With Poor Short-Term Outcomes in Patients With Acute Decompensated Heart Failure. Mo R, Yang YM, Yu LT, Tan HQ, Zhu J. Front Cardiovasc Med. 2021 Mar 11;8:629268. doi: 10.3389/fcvm.2021.629268. PMID: 33778022; PMCID: PMC7990871.
- An Overview of FGF-23 as a Novel Candidate Biomarker of Cardiovascular Risk. Vázquez-Sánchez S, Poveda J, Navarro-García JA, González-Lafuente L, Rodríguez-Sánchez E, Ruilope LM, Ruiz-Hurtado G. Front Physiol. 2021 Mar 9;12:632260. doi: 10.3389/fphys.2021.632260. PMID: 33767635; PMCID: PMC7985069.
- Discharge FGF23 level predicts one year outcome in patients admitted with acute heart failure. Vergaro G, Aimo A, Taurino E, Del Franco A, Fabiani I, Prontera C, Masotti S, Musetti V, Emdin M, Passino C. Int J Cardiol. 2021 Aug 1;336:98-104. doi: 10.1016/j.ijcard.2021.05.028. Epub 2021 May 19. PMID: 34019969.
- Endostatin in Renal and Cardiovascular Diseases. Li M, Popovic Z, Chu C, Krämer BK, Hocher B. Kidney Dis (Basel). 2021 Sep 9;7(6):468-481. doi: 10.1159/000518221. PMID: 34901193; PMCID: PMC8613550.
- Association between endostatin and mortality in patients with acute dyspnoea, with or without congestive heart failure: a single-centre, prospective, observational study. Yaghoubi A, Heijl C, Khoshnood AM, Wändell PE, Carlsson AC, Wessman T. BMJ Open. 2025 Jan 11;15(1):e085238. doi: 10.1136/bmjopen-2024-085238. PMID: 39800400; PMCID: PMC11752042.
- Leucine-Rich Alpha-2-Glycoprotein: A Novel Predictor of Diastolic Dysfunction. Loch A, Tan KL, Danaee M, Idris I, Ng ML. Biomedicines. 2023 Mar 20;11(3):944. doi: 10.3390/biomedicines11030944. PMID: 36979923; PMCID: PMC10045934.
- Immune response to lipoproteins in atherosclerosis. Samson S, Mundkur L, Kakkar VV. 2012;2012:571846. doi: 10.1155/2012/571846. Epub 2012 Aug 23. PMID: 22957222; PMCID: PMC3432325.
- Antibodies against human oxidized low-density lipoprotein (LDL) as markers for human plasma modified lipoproteins. Radulescu L, Stancu C, Antohe F. Med Sci Monit. 2004 Jul;10(7):BR207-14. Epub 2004 Jun 29. PMID: 15232494.
- Oxidized LDL and anti-oxidized LDL antibodies in atherosclerosis – Novel insights and future directions in diagnosis and therapy .Hartley A, Haskard D, Khamis R. Trends Cardiovasc Med. 2019 Jan;29(1):22-26. doi: 10.1016/j.tcm.2018.05.010. Epub 2018 Jun 4. PMID: 29934015.
- IL-6 and Cardiovascular Risk: A Narrative Review. Mehta NN, deGoma E, Shapiro MD. Curr Atheroscler Rep. 2024 Nov 26;27(1):12. doi: 10.1007/s11883-024-01259-7. PMID: 39589436; PMCID: PMC11599326.
- Interleukin-6 Signaling and Anti-Interleukin-6 Therapeutics in Cardiovascular Disease. Ridker PM, Rane M. Circ Res. 2021 May 28;128(11):1728-1746. doi: 10.1161/CIRCRESAHA.121.319077. Epub 2021 May 17. PMID: 33998272.
Effect of left atrial appendage closure on heart failure biomarker NT-proANP.
Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia, affecting about 1-2% of the general population. The incidence of AF increases with age and AF carries a five-fold increased risk of cardioembolic events, accounting for roughly 20% of all strokes. Strokes related to AF tend to be more severe, often resulting in worse neurological outcomes (1).
The left atrial appendage (LAA) is a finger-shaped extension originating from the main body of the left atrium. In AF, thrombus formation often occurs within the LAA due to decreased contractile function and blood flow stasis. 90% of thrombi in nonvalvular AF patients and 57% in valvular AF patients are located in the left atrial appendage (LAA). Though oral anticoagulants serve as the primary treatment for preventing strokes in patients with atrial fibrillation, they are not suitable for all patients due to certain contraindications. Targeting the LAA has emerged as an alternative treatment approach to decrease the risk of stroke or systemic embolism in patients with atrial fibrillation (2-5).
In a study published in 2024, researchers investigated the impact of left atrial appendage (LAA) closure on systemic homeostasis in patients with atrial fibrillation. The study aimed to understand how occluding the LAA influences systemic biomarkers related to coagulation, inflammation, and endothelial function. Results suggest that LAA closure not only reduces stroke risk but may also favorably modulate systemic physiological processes, potentially contributing to improved overall cardiovascular health in these patients (5).
Effect of left atrial appendage closure on heart failure biomarker NT-proANP
In the subanalysis of this trial, researchers also examined the effects of left atrial appendage (LAA) closure on heart failure biomarkers, including NT-proBNP, NT-proANP, Galectin-3, and GDF-15 in patients with atrial fibrillation. The results demonstrated that LAA closure did not significantly influence the levels of HF biomarkers 6 months after the procedure. (6).
In a recent study researchers investigated the hemodynamic and echocardiography changes during and after LAA closure (7). Biomarkers for heart failure were measured including, N-terminal pro-B-type natriuretic peptide (NT-proBNP), N-terminal-pro-atrial natriuretic peptide (NT-proANP) and growth-differentiation factor-15 (GDF-15). The results show that LAA Closure was associated with an acute increase in both rest and postexercise LA pressure. The acute changes during LAAC were explained mostly by the saline and contrast dye given during LAAC and not by the worsening of the reservoir function associated with the procedure. In addition, no increase in NT-proANP and other HF biomarkers or changes in echocardiography parameters after 3 or 6 months after the procedure were observed (7).
About NT-proANP
NT-proANP (N-terminal pro-atrial natriuretic peptide) is a biomarker derived from the precursor of atrial natriuretic peptide (ANP), a hormone produced primarily by the atria of the heart. It plays a key role in regulating blood pressure, blood volume, and electrolyte balance by promoting natriuresis (excretion of sodium) and vasodilation.
Elevated levels of NT-proANP are often associated with conditions involving increased atrial pressure and volume overload, such as heart failure, atrial fibrillation, and other cardiac dysfunctions. Because it is relatively stable and easier to measure than active ANP, NT-proANP is frequently used in clinical settings to assess and monitor cardiac function.
About NT-proBNP
NT-proBNP (N-terminal pro-B-type natriuretic peptide) is a biomarker released from the heart in response to increased wall stress, typically due to conditions like heart failure. It is a non-active fragment of the prohormone BNP (B-type natriuretic peptide), which is produced mainly by the ventricles of the heart when they are under strain.
Elevated levels of NT-proBNP are indicative of cardiac stress and are commonly used in clinical practice to diagnose, assess the severity, and monitor the progression of heart failure. It also helps differentiate cardiac from non-cardiac causes of symptoms such as shortness of breath. Because NT-proBNP is stable in blood samples and has a longer half-life than BNP, it is a reliable biomarker for evaluating cardiac function across various clinical settings.
NT proANP ELISA (cat. No. BI-20892) Assay Kit
- CONVENIENT – small sample volume – 10 µl / well
- HIGH QUALITY kit – full validation package
- TRUSTED – cited in over 175 publications
- EASY – color coded and ready to use reagents
- FLEXIBLE- assay is suitable for human and non-human samples (rodents and others)
NT-proBNP (cat. no. SK-1204) ELISA Assay Kit
- TRUSTED – widely cited in over 140 publications
- HIGH QUALITY kit – fully validated assays following international quality guidelines
- CONVENIENT – kits include pre-diluted calibrators and 2 controls
RAT NT-proBNP ELISA (BI-1204R) Assay Kit
- CONVENIENT – 10µl sample/well, kit control included
- TRUSTED – sample values provided
Example of Biomedica ELISA Assay kit box and Reagent Set
Literature
- Left Atrial Appendage Closure and Systemic Homeostasis: The LAA HOMEOSTASIS Study. Lakkireddy D, Turagam M, Afzal MR, Rajasingh J, Atkins D, Dawn B, Di Biase L, Bartus K, Kar S, Natale A, Holmes DJ Jr.J Am Coll Cardiol. 2018 Jan 16;71(2):135-144. doi: 10.1016/j.jacc.2017.10.092. Erratum in: J Am Coll Cardiol. 2018 Feb 6;71(5):590. doi: 10.1016/j.jacc.2018.01.005. PMID: 29325636.
- The Left Atrial Appendage: Target for Stroke Reduction in Atrial Fibrillation. Ramlawi B, Abu Saleh WK, Edgerton J. Methodist Debakey Cardiovasc J. 2015 Apr-Jun;11(2):100-3. doi: 10.14797/mdcj-11-2-100. PMID: 26306127; PMCID: PMC4547664.
- The left atrial appendage: anatomy, function, and noninvasive evaluation. Beigel R, Wunderlich NC, Ho SY, Arsanjani R, Siegel RJ. JACC Cardiovasc Imaging. 2014 Dec;7(12):1251-65. doi: 10.1016/j.jcmg.2014.08.009. PMID: 25496544.
- Left atrial appendage exclusion in atrial fibrillation. Rozen G, Margolis G, Marai I, Roguin A, Rahamim E, Planer D, Heist EK, Amir O, Tahiroglu I, Ruskin J, Mansour M, Elbaz-Greener G. Front Cardiovasc Med. 2022 Sep 13;9:949732. doi: 10.3389/fcvm.2022.949732. PMID: 36176999; PMCID: PMC9513198.
- Left atrial appendage closure for stroke prevention in atrial fibrillation: current status and perspectives. Landmesser U, Skurk C, Tzikas A, Falk V, Reddy VY, Windecker S. Eur Heart J. 2024 Aug 21;45(32):2914-2932. doi: 10.1093/eurheartj/ehae398. PMID: 39027946; PMCID: PMC11335376.
- The effect of left atrial appendage closure on heart failure biomarkers: A PRAGUE-17 trial subanalysis. Herman D, Osmancik P, Neuzil P, Hala P, Lekesova V, Benesova K, Hozman M, Jarkovsky J, Novackova M, Widimsky P, Reddy VY; PRAGUE-17 Trial Investigators. J Cardiovasc Electrophysiol. 2021 Oct;32(10):2645-2654. doi: 10.1111/jce.15206. Epub 2021 Aug 26. PMID: 34402135.
- Acute and Short‐Term Hemodynamic and Echocardiography Changes During and After Left Atrial Appendage Closure. Dalibor Herman, Petr Peichl, Marek Hozman, Bronislav Janek, Tomas Knize, Teodora Vichova, Hana Linkova, Jana Vesela, Jakub Karch, Naďa Valosková, Eva Borisincova, Pavel Osmancik, J Interventional Cardiology, Dec. 2025. https://doi.org/10.1155/joic/5515180Digital Object Identifier (DOI)
microbial–metabolic signatures associated with plaque destabilization and resolution
Coronary artery disease (CAD) is the primary cause of death worldwide (1). Clinical manifestations of CAD are divided into chronic or stable CAD (sCAD), characterized by gradual artery narrowing, and acute coronary syndromes (ACS), which involve a sudden interruption of blood flow (2).
The human gut hosts trillions of microbes, known as the gut microbiota, which play key roles in metabolism and immune regulation. Its composition, influenced by environment and genetics, and changes in the gut microbiota have been linked to CAD development. Microbial metabolites can also enter circulation and contribute to CAD pathology (3).
Gut-Heart Axis in Coronary Artery Disease
In a recent study researchers explored the role of the gut-heart axis in coronary artery disease: Distinct microbial and metabolic shifts characterize acute coronary syndrome and recovery. Xu J et al., Imeta. 2025.
Key highlights:
- Changes in the gut microbiome are closely linked to CAD progression.
- Changes are observed across normal coronary arteries, stable CAD, and acute coronary syndrome (ACS).
- Multi-omics machine learning models effectively differentiated CAD subtypes, outperforming traditional clinical risk factors.
Our human NT-proBNP assay was featured in this study.
NT-proBNP ELISA (cat. no. SK-1204)
√ CONVENIENT – can be used in every lab
√ RELIABLE – Full validation package
√ EASY – 5 pre-diluted standards and 2 controls included
√ TRUSTED – Widely cited in more than 140 publications
Literature
- Global prevalence of coronary artery disease: an update from the global burden of disease study. Stark, B, Johnson, C, Roth, G. JACC.2024 Apr, 83 (13_Supplement) 2320.
- Acute and chronic coronary artery disease. Lancellotti P. Acta Cardiol. 2024 Apr;79(2):105-108. PMID: 38628088.
- The role of gut microbiota in cardiovascular diseases and their potential as novel therapeutic targets. Yamashita T. J Cardiol. 2025 Aug;86(2):141-147. doi: 10.1016/j.jjcc.2025.05.002. Epub 2025 May 21. PMID: 40409712.
- Distinct microbial and metabolic shifts characterize acute coronary syndrome and recovery. Xu J et al., Imeta. 2025 Sep 19;4(5):e70079. PMID: 41112052.
Insights from animal models and MSC transplantation
Pulmonary Veno-Occlusive Disease (PVOD), also known as “pulmonary arterial hypertension (PAH), is a rare form of pulmonary hypertension. It is caused by progressive blockage of small veins in the lungs leading to increased pressure followed by right-sided heart failure (1). As effective treatments are limited, lung transplantation remains the only available option. There is no effective medical treatment and lung transplantation is the only curative option. The prognosis is unfavorable, with an average life expectancy of two years following onset of symptoms (2).
Developing PVOD-Specific Therapies
In a recent study researchers investigated the impact of allogeneic mesenchymal stem cell (ASCs) transplantation on lung tissue and its potential in reducing pulmonary hypertension in a rat model of PVOD. Additionally, they assessed whether this intervention contributes to the improvement of right ventricular hypertrophy (3). Continued and future research involving animal models alongside patient samples offers hope for developing PVOD-specific therapies that can prevent and/or treat the disease (4).
Abstract
Background: Pulmonary veno-occlusive disease (PVOD) is a rare subtype of disease that causes pulmonary hypertension with vascular involvement of postcapillary structures of pulmonary vasculature. The disease has a poor prognosis with no effective therapy. The study aimed to determine whether adipose-derived mesenchymal stem cells (ASCs) alleviate pulmonary hypertension and right ventricular hypertrophy in a rat model of PVOD.
Methods: Allogeneic ASCs were intravenously administered to a rat model of PVOD induced by mitomycin C. Then, muscularization in pulmonary microvessels, right ventricular systolic pressure (RVSP), and right ventricular hypertrophy were assessed using immunohistochemistry, right heart catheterization, heart weight, and hematoxylin–eosin (HE) staining. Body weight over time and survival rates were assessed.
Results: ASC transplantation substantially contributed to the reduction of pulmonary microvascular muscularization in the PVOD rat model but not to the decrease in RVSP. Furthermore, it led to the attenuation of right ventricular hypertrophy and a considerable decrease in wall thickness. However, repeated ASC administration increased the mortality rate in the PVOD rat models.
Conclusions: To the best of our knowledge, this is the first study to analyze the effects of ASC transplantation in a rat model of PVOD. While intravenous ASC transplantation exerts beneficial effects on the lungs and right ventricle, adverse events may occur depending on the administration method. Therefore, intravenous ASC transplantation should be performed with caution.
NT-proBNP measurements were successfully performed in the PVOD rat model in rat serum utilizing our Rat NT-proBNP ELISA assay.
Rat NT-pro BNP ELISA assay (cat. no. BI-1204R)
- Efficient – only 10 µl / well sample
- Accurate – kit control included – protocol booklet click here
- Reliable – sample values provided – validation data click here
- Trusted – cited using various rat models – citations click here
Read our first independant review
Rat NT-proBNP ELISA assay
Related products:
NT-proANP ELISA Assay (cat. no. BI-20892)
Literature:
- Diagnosis and management of pulmonary veno-occlusive disease. Solinas S, Boucly A, Beurnier A, Kularatne M, Grynblat J, Eyries M, Dorfmüller P, Sitbon O, Humbert M, Montani D. Expert Rev Respir Med. 2023 Jul-Dec;17(8):635-649. doi: 10.1080/17476348.2023.2247989. Epub 2023 Aug 21. PMID: 37578057.
- Pulmonary Veno-Occlusive Disease. Siddiqui NA, Charoenpong P. 2023 Jul 31. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan–. PMID: 36256776.
- Intravenous mesenchymal stem cell transplantation mitigates pulmonary vascular remodeling but poses dose related risks in a pulmonary veno-occlusive disease model. Katagiri J, Homma J, Takagi R, Sekine H, Shinkawa T, Niinami H, Shimizu T.Stem Cell Res Ther. 2025 May 28;16(1):258. doi: 10.1186/s13287-025-04400-8. PMID: 40437633; PMCID: PMC12121274.
- Pulmonary veno-occlusive disease: Insights from animal models. Hata A, Gur B, Kalra J, Prabhakar A. Vascul Pharmacol. 2025 Sep 10;161:107547. doi: 10.1016/j.vph.2025.107547. Epub ahead of print. PMID: 40939813.