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big Endothelin ELISA

Direct measurement! - CE marked - for IVD use in EU!


Assay characteristics:

Cat.No.: BI-20082H
Method: Sandwich ELISA, HRP/TMB, 12x8-well strips
Sample type:Serum, plasma (EDTA, heparin, citrate)
Standard range:0-3 pmol/l (6 serum based standards)
Standard points:0/0.1/0.2/0.4/1/3 pmol/l
Control:1 serum based control
Sample size:50 µl / well
Incubation time:4 h / 1 h / 30 min
Unit conversion:1 pg/ml = 0.2335 fmol/ml (MW: 4.283 kDa)

LOD: 0.02 pmol/l (0 pmol/l + 3 SD)

Intra-assay (n=5) ≤ 5%, Inter-assay (n=10) ≤ 4%

The mean recovery of recombinant Big ET (spike 1 pmol/l; 2 pmol/l) is: 
Serum (n=14): 98%; 105% 
EDTA plasma (n=3) : 101%; 105%
Heparin plasma (n=3): 98%; 102%
Citrate plasma (n=3): 99%; 105% 

Dilution linearity:
The mean dilution linearity of endogenous Big ET with a low measuring human serum is:
For a 1+1 dilution = 90%
For a 1+3 dilution = 96%
For a 1+7 dilution = 98%

Cross reactivity:
ET1/2/3 (1-21): <1%, ET2 (1-37): <1%, ET1/2 (1-38): <1%, porcine BigET (1-39): 21%, BigET1/2 (22-38): <1%, BigET2 (22-37): <1%, rat BigET1 (1-39): 10%, Sarafotoxin: <1%

Values from apparently healthy individuals:
Median (serum, n=41): 0.09 pmol/l
It is recommended to establish the normal range for each laboratory.

Principle of the assay: 

Manual ELISAs - easily adaptable for automation! 

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BI-20082H Big Endothelin ELISA IFU CE version

BI-20082H Big Endothelin ELISA IFU RUO version

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Click link for Big ET Validation Data (stability, S/R, dilution linearity, precision,..).

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Big Endothelin-1 (BigET) is a peptide of 38 amino acids and is the precursor of Endothelin-1 (ET), represented by amino acids 1-21 ( ET is a potent vasoconstrictor and is produced by vascular endothelial cells. Accordingly it has a wide tissue distribution ( The cleavage of BigET by Endothelin Converting Enzyme (ECE) leads to ET and to a C-terminal fragment. Both BigET and ET are strong independent predictors of survival in patients with congestive heart failure, and identify a population with a very high risk mortality. The half-life of ET (1-21) in plasma is less than one minute, whereas clearance of BigET is much slower. BigET can therefore be determined more easily.

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BI-20082H Big ET ELISA Reference List

BI-20082H Big ET ELISA Citations in Cardiology 

Renal function, N-terminal Pro-B-Type natriuretic peptide, propeptide big-endothelin and patients with heart failure and preserved ejection fraction.
Gergei I, Krämer BK, Scharnagl H, Stojakovic T, März W.
2018 Apr 21.
PMID: 29684593

Study population: Patients with coronary artery disease (CAD, n=439)
Sample Type: EDTA plasma
Conclusions: “In general, NT-proBNP is a good indicator of suspected heart failure. While for NT-proBNP different cut-off points have to be considered in the diagnosis of HFpEF, a single cut-off point of Big-ET-1 was appropriate in the diagnosis of HFpEF, regardless of the presence or absence of CKD. An additional measurement of Big-ET-1 improves the diagnosis of HFpEF in patients with chronic kidney disease.” 

Association of baseline big endothelin-1 level with long-term prognosis among cardiac resynchronization therapy recipients.
Yang S, Liu Z, Liu S, Ding L, Chen K, Hua W, Zhang S.
Clin Biochem. 2018. pii: S0009-9120(17)31071-8.

Study population: Patients with or without CRT (CAD, n=367)
Sample Type: EDTA plasma
Conclusions: “Baseline big ET-1 > 0.56 pmol/L was independently associated with higher all-cause mortality and HFH among CRT recipients, and therefore can be added to the marker panel used for stratifying high risk CRT patients for priority treatment.”

Predictive value of big endothelin-1 on outcomes in patients with myocardial infarction younger than 35 years old.
Zhou BY, Gao XY, Zhao X, Qing P, Zhu CG, Wu NQ, Guo YL, Gao Y, Liu G, Dong Q, Li JJ. Per Med. 2018 Jan;15(1):25-33.
PMID: 29714117.

Study population: Patients with myocardial infarction (MI, n=565)
Sample Type: EDTA plasma
Conclusions: “The study first demonstrated that big ET-1 was an independent predictor for major adverse cardiovascular events (MACEs) in MI patients younger than 35 years old.

Big endothelin-1 level is a useful marker for predicting the presence of isolated coronary artery ectasia.
Wang Y, Zhang Y, Zhu CG, Guo YL, Huang QJ, Wu NQ, Gao Y, Qing P, Liu G, Dong Q, Li JJ.
Biomarkers. 2017 May - Jun;22(3-4):331-336.
PubMed PMID: 27885846.

Study population: Patients with coronary artery disease (CAD, n=216)
Sample Type: EDTA plasma
Conclusions: “The level of plasma big ET-1 was significantly higher in patients with isolated coronary artery ectasia (CAE, p
<0.001) […] Big ET-1 may be a useful predictor for the presence of isolated CAE.

The association between plasma big endothelin-1 levels at admission and long-term outcomes in patients with atrial fibrillation.
Wu S, Yang YM, Zhu J, Ren JM, Wang J, Zhang H, Shao XH.
Atherosclerosis. 2018 May; 272:1-7.
PMID: 29529394.

Study population: Patients with atrial fibrillation (AF, n=716)
Sample Type: EDTA plasma
Conclusions: “Elevated big ET-1 levels is an independent predictor of long-term all-cause mortality, MAEs, and cardiovascular death in patients with AF.

Influence of Mechanical Circulatory Support on Endothelin Receptor Expression in Human Left Ventricular Myocardium from Patients with Dilated Cardiomyopathy (DCM). 
Gärtner F, Abraham G, Kassner A, Baurichter D, Milting H.
PLoS One. 2017 Jan 17;12(1):e0169896.
PubMed PMID: 28095452

Study population: Patients dilated cardiomyopathy (n=12)
Sample Type: Plasma
Conclusions: “
Plasma Big-ET1 is significantly lower (p < 0.05, t-Test) after 28 ± 11 days of ventricular assist devices (VAD)-support compared to the time of VAD-implantation. There is no evidence for a correlation of myocardial ETA or ETB receptor density and plasma Big-ET1

Propeptide big-endothelin, N-terminal-pro brain natriuretic peptide and mortality. The Ludwigshafen risk and cardiovascular health (LURIC) study.
Gergei I, Krämer BK, Scharnagl H, Stojakovic T, März W, Mondorf U.
Biomarkers. 2017 May -Jun;22(3-4):315-320.
PMID: 27788598.

Study population: Patients referred for coronary angiography (n=2829)
Sample Type: EDTA Plasma
Conclusions: “The conjunct use of Big-ET-1 and NT-proBNP improves the risk stratification of patients with intermediate to high risk of cardiovascular (CV) disease and congestive heart failure (CHF).”

Plasma level of big endothelin-1 predicts the prognosis in patients with hypertrophic cardiomyopathy.
Yilu Wang, Yida Tang, Yubao Zou, DongWang, Ling Zhu, Tao Tian, JizhengWang, Jingru Bao, Rutai Hui , Lianming Kang, Lei Song, Ji Wang
Int J Cardiol (2017).

PMID: 26565974

Study population: Patients with HCM (n=245)
Sample Type: EDTA plasma
Conclusions: “
high level of plasma big endothelin-1 predicted prognosis for patients with HCM and it can be added to the marker panel in stratifying HCM patients for giving treatment priority to those at high risk.

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.
PMID: 28038820.

Study population: Patients with stable coronary artery disease (CAD, n=3154)
Sample Type: EDTA plasma
Conclusions: “
The present study firstly suggests that big ET-1 is an independent risk marker of cardiovascular outcomes in patients with stable CAD.

Associations of big endothelin-1 and C-reactive protein in atrial fibrillation.
Zheng L-H, Sun W, Yao Y, Hou B-B, Qiao Y, Zhang S.
Journal of Geriatric Cardiology: JGC. 2016;13(5):465-470.
PMCID: PMC4984574

Study population: Patients with atrial fibrillation (AF, n=128)
Sample Type: Plasma
Conclusions: “Both plasma hs-CRP and big ET-1 levels are elevated in lone AF patients, and are associated with AF. In paroxysmal lone AF patients, there were significant positive correlations between plasma hs-CRP level and big ET-1 level. 

The role of circulating thrombospondin-1 in patients with precapillary pulmonary hypertension.
Kaiser R, Frantz C, Bals R, Wilkens H.

Respir Res. 2016 Jul 30;17(1):96.
PMID: 27473366

Study population: Patients with pulmonary hypertension (PH, n=293)
Sample Type: Citrate plasma
Conclusions: “Big-endothelin showed significantly increased levels in both pulmonary arterial hypertension (PAH) and chronic thromboembolic PH (CTEPH) patients, while levels in the group with lung disease associated PH (LD) did not reach statistical significance.”

Predictive Values of N-Terminal Pro-B-Type Natriuretic Peptide and Cardiac Troponin I for Myocardial Fibrosis in Hypertrophic Obstructive Cardiomyopathy.
Zhang C, Liu R, Yuan J, Cui J, Hu F, Yang W, Zhang Y, Chen Y, Qiao S.
PLoS One. 2016 Jan 14;11(1):e0146572.
PMID: 26765106

Study population: Patients with hypertrophic obstructive cardiomyopathy (HOCM, n=163)
Sample Type: Plasma
Conclusions: “Serum cTnI is an independent predictor useful for identifying myocardial fibrosis, while plasma NT-proBNP is only associated with myocardial fibrosis on univariate analysis. Combined measurements of serum cTnI with MWT further improve its value in detecting myocardial fibrosis in patients with HOCM.

Clinical and prognostic value of endothelin-1 and big endothelin-1 expression in children with pulmonary hypertension.
Latus H, Karanatsios G, Basan U, Salser K, Müller S, Khalil M, Kreuder J, Schranz D, Apitz C.
2016 Jul 1;102(13):1052-8.
PMID: 26955847.

Study population: Patients with pulmonary arterial hypertension (PH, n=66)
Sample Type: Plasma
Conclusions: “Although children with PH had alterations in ET-1/big ET-1 expression, which may reflect changes in net release or lung clearance, levels of ET-1/big ET-1 showed no correlation with clinical and haemodynamic parameters, and were not able to predict outcome.

Plasma level of big endothelin-1 predicts the prognosis in patients with hypertrophic cardiomyopathy.
Yilu Wang, Yida Tang, Yubao Zou, DongWang, Ling Zhu, Tao Tian, JizhengWang, Jingru Bao, Rutai Hui , Lianming Kang, Lei Song, Ji Wang
Int J Cardiol (2017).

PMID: 26565974

Study population: Patients with HCM (n=245)
Sample Type: plasma
Conclusions: “
high level of plasma big endothelin-1 predicted prognosis for patients with HCM and it can be added to the marker panel in stratifying HCM patients for giving treatment priority to those at high risk.

Association of Big Endothelin-1 with Coronary Artery Calcification.
Qing P, Li XL, Zhang Y, Li YL, Xu RX, Guo YL, Li S, Wu NQ, Li JJ.
PLoS One. 2015 Nov 13;10(11):e0142458.
PMID: 26565974

Study population: Patients with coronary artery calcification (CAC, n=510)
Sample Type: Plasma
Conclusions: “The data firstly demonstrated that the plasma big ET-1 level was a valuable independent predictor for CAC in our study.

Plasma Big Endothelin-1 Level and the Severity of New-onset Stable Coronary Artery Disease.

Chen J1, Chen MH, Guo YL, Zhu CG, Xu RX, Dong Q, Li JJ.
J Atheroscler Thromb. 2015;22(2):126-35.
PMID: 25195814

Study population: consecutive stable CAD patients (n=963)
Sample Type: Plasma
Conclusions: “The present findings indicate that the plasma big ET-1 level is a useful predictor of the severity of new-onset stable CAD associated with significant stenosis.

Plasma NT pro-BNP, hs-CRP and big-ET levels at admission as prognostic markers of survival in hospitalized patients with dilated cardiomyopathy: a single-center cohort study.
Li X, Chen C, Gan F, Wang Y, Ding L, Hua W.
BMC Cardiovasc Disord. 2014 May 11;14:67.
PMID: 24885051

Study population: Patients with dilated cardiomyopathy (DCM, n=622)
Sample Type: Plasma
Conclusions: “In a large population of patients with DCM, the circulating concentrations of NT pro-BNP and hs-CRP, but not big-ET, were independent markers of all-cause mortality.”

Plasma soluble ST2 levels correlate with disease severity and predict clinical worsening in patients with pulmonary arterial hypertension.
Zheng YG, Yang T, He JG, Chen G, Liu ZH, Xiong CM, Gu Q, Ni XH, Zhao ZH.
Clin Cardiol. 2014 Jun;37(6):365-70.
PMID: 25068163.

Study population: Patients with pulmonary arterial hypertension (PAH, n=40)
Sample Type: Plasma
Conclusions: “We found that plasma sST2 levels were elevated in idiopathic PAH patients, and sST2 levels correlated with hemodynamic parameters and other biomarkers, including uric acid and Big ET1. Our results also suggested that the elevation of sST2 levels was associated with worse clinical outcomes.”

Different populations of circulating endothelial cells in patients with age-related macular degeneration: a novel insight into pathogenesis.
Machalinska A, Safranow K, Dziedziejko V, Mozolewska-Piotrowska K, Paczkowska E, Klos P, Pius E, Grymula K, Wiszniewska B, Karczewicz D, Machalinski B.
Invest Ophthalmol Vis Sci. 2011 Jan 5;52(1):93-100.
PMID: 20720219.

Study population: patients with the neovascular form of age-related macular degeneration (AMD, n=29), healthy controls (n=38)
Sample Type: EDTA Plasma
Conclusions: “Increased circulating endothelial cells (CECs) and endothelial progenitor cells (EPCs) were found in the AMD patients compared with the counts in healthy individuals. The expression of intracellular ET-1 was significantly elevated in PBNCs from the AMD patients compared with the control subjects. In addition, a significantly higher plasma concentration of IGF-1 was observed, but a lower SDF-1 level in the group of AMD patients. circulating endothelial cells, together with high ET-1 content, may contribute to the development of AMD.

TNFalpha-induced GM-CSF release from human airway smooth muscle cells depends on activation of an ET-1 autoregulatory positive feedback mechanism.
Knobloch J, Peters H, Jungck D, Müller K, Strauch J, Koch A.
Thorax. 2009 Dec;64(12):1044-52.
PMID: 19850966.

Study population: Human pulmonary arteries from healthy segments of lung
Sample Type: Cell line
Conclusions: “TNF-a activates an ETAR- and p38MAPK-dependent ET-1 autoregulatory positive feedback loop to maintain GM-CSF release from HASMCs. Since bosentan impairs ET-1 autoregulation and TNFa-induced ET-1 release, as well as TNFa- and ET-1-induced GM-CSF release, the present data suggest therapeutic utility for bosentan in treating particularly the early stages of chronic inflammatory airway diseases.

Synergistic Induction of Endothelin-1 by Tumor Necrosis Factor α and Interferon γ Is due to Enhanced NF-κB Binding and Histone Acetylation at Specific κB Sites.
The Journal of Biological Chemistry. 2009;284(36):24297-24305.
Wort SJ, Ito M, Chou PC, Mc Master SK, Badiger R, Jazrawi E, de Souza P, Evans
TW, Mitchell JA, Pinhu L, Ito K, Adcock IM.

PMCID: PMC2782023.

Study population: Human pulmonary arteries from healthy segments of lung
Sample Type: Cell supernatent
Conclusions: “Here we demonstrate synergistic induction of preproET-1 message RNA and release of mature peptide by a combination of tumor necrosis factor alpha (TNFalpha) and interferon gamma (IFNgamma) in primary human pulmonary artery smooth muscle cells. This induction was prevented by pretreatment with the histone acetyltransferase inhibitor anacardic acid. TNFalpha induced a rapid and prolonged pattern of nuclear factor (NF)-kappaB p65 subunit activation and binding to the native preproET-1 promoter. In contrast, IFNgamma induced a delayed activation of interferon regulatory factor-1 without any effect on NF-kappaB p65 nuclear localization or consensus DNA binding. However, we found cooperative p65 binding and histone H4 acetylation at distinct kappaB sites in the preproET-1 promoter after stimulation with both TNFalpha and IFNgamma. This was associated with enhanced recruitment of RNA polymerase II to the ATG start site and read-through of the ET-1 coding region. Understanding such mechanisms is crucial in determining the key control points in ET-1 release.”

Elevation of circulating big endothelin-1: an independent prognostic factor for tumor recurrence and survival in patients with esophageal squamous cell carcinoma.
Jiao W, Xu J, Zheng J, Shen Y, Lin L, Li J.
BMC Cancer. 2008 Nov 15;8:334.
PMID: 19014602

Study population: Patients with esophageal squamous cell carcinoma (ESCC, n=108)
Sample Type: Cell supernatent
Conclusions: “Plasma big ET-1 level in ESCC patients may reflect malignancy and predict tumor recurrence and patient survival. Therefore, the preoperative plasma big ET-1 levels may be a clinically useful biomarker for choice of multimodality therapy in ESCC patients.”

Particulate matter exposure induces persistent lung inflammation and endothelial dysfunction.
Tamagawa E, Bai N, Morimoto K, Gray C, Mui T, Yatera K, Zhang X, Xing L, Li Y, Laher I, Sin DD, Man SF, van Eeden SF.
Am J Physiol Lung Cell Mol Physiol. 2008 Jul;295(1):L79-85.
PMID: 18469117

Study population: Human pulmonary arteries from healthy segments of lung
Sample Type: Cell supernatent
Conclusions: “[…] particulate matter air pollution (PM) is a risk factor for the development of atherosclerosis. […] PM-induced lung and systemic inflammatory responses contribute to the adverse vascular events associated with exposure to air pollution.”

The peptidase inhibitor CGS-26303 increases endothelin converting enzyme-1 expression in endothelial cells through accumulation of big endothelin-1.
Raoch V, Martinez-Miguel P, Arribas-Gomez I, Rodriguez-Puyol M, Rodriguez-Puyol D, Lopez-Ongil S.
Br J Pharmacol. 2007 Oct;152(3):313-22.
PMID: 17643133

Study population: Bovine aortic endothelial cells
Sample Type: Cell supernatent
Conclusions: “These results suggest that the accumulation of big ET-1 is responsible for the effects of CGS-26303 on ECE-1 and they did not depend on NEP blockade. Changes in ECE-1 protein after the administration of CGS-26303 could lead to a decreased response in long-term treatments.”

Cell-type specific interaction of endothelin and the nitric oxide system: pattern of prepro-ET-1 expression in kidneys of L-NAME treated prepro-ET-1 promoter-lacZ-transgenic mice.
Slowinski T, Kalk P, Christian M, Schmager F, Relle K, Godes M, Funke-Kaiser H, Neumayer HH, Bauer C, Theuring F, Hocher B.
J Physiol.
2007 Jun 15;581(Pt 3):1173-81.
PMID: 17395629

Study population: Prepro-ET-1 lacZ transgenic mice
Sample Type: Cell supernatent
Conclusions: “In conclusion, our study revealed a close interaction of renal endothelin and the NO system in a cell-type specific manner.”

Constitutive ALK5-independent c-Jun N-terminal kinase activation contributes to endothelin-1 overexpression in pulmonary fibrosis: evidence of an autocrine endothelin loop operating through the endothelin A and B receptors.
Shi-Wen X, Rodríguez-Pascual F, Lamas S, Holmes A, Howat S, Pearson JD, Dashwood MR, du Bois RM, Denton CP, Black CM, Abraham DJ, Leask A.
Mol Cell Biol. 2006 Jul;26(14):5518-27.

PMID: 16809784

Study population: normal and SSc lung fibroblasts
Sample Type: Cell supernatent
Conclusions: “TGF-β induces ET-1 in normal and fibrotic lung fibroblasts in a Smad-independent ALK5/c-Jun N-terminal kinase (JNK)/Ap-1-dependent fashion. ET-1 induces JNK through TAK1. Fibrotic lung fibroblasts display constitutive JNK activation, which was reduced by the dual ETA/ETB receptor inhibitor, bosentan, providing evidence of an autocrine endothelin loop. Thus, ET-1 and TGF-β are likely to cooperate in the pathogenesis of pulmonary fibrosis.”

Val-HeFT investigators. The prognostic value of big endothelin-1 in more than 2,300 patients with heart failure enrolled in the Valsartan Heart Failure Trial (Val-HeFT).
Masson S, Latini R, Anand IS, Barlera S, Judd D, Salio M, Perticone F, Perini G, Tognoni G, Cohn JN.
J Card Fail. 2006 Jun;12(5):375-80.

PMID: 16762801.

Study population: patients with stable, symptomatic heart failure (HF), who were on prescribed HF therapy (n= 2359)
Sample Type: Plasma
Conclusions: “In a large population of patients with symptomatic heart failure, the circulating concentration of Big ET-1, a precursor of the paracrine and bioactive peptide ET-1, was an independent marker of mortality and morbidity. In this setting, BNP remained the strongest neurohormonal prognostic factor.”

Immunoluminometric assay for measurement of the C-terminal endothelin-1 precursor fragment in human plasma. 
Papassotiriou J, Morgenthaler NG, Struck J, Alonso C, Bergmann A.
Clin Chem. 2006 Jun;52(6):1144-51.

PMID: 16627560.

Study population: healthy individuals (n=326), patients with congestive heart failure (CHF, n=77), and patients with sepsis (n=116)
Sample Type: EDTA Plasma
Conclusions: “CT-proET-1 measurement is a rapid and easy method for indirectly assessing the release of ET-1 in critically ill patients.”

Systemic endothelial dysfunction in adults with cyanotic congenital heart
Oechslin E, Kiowski W, Schindler R, Bernheim A, Julius B, Brunner-La Rocca HP.
Circulation. 2005 Aug 23;112(8):1106-12.
PMID: 16103236.

Study population: patients with congenital heart disease (CCHD, n=11), healthy individuals (n=10)
Sample Type: EDTA Plasma
Conclusions: “Systemic endothelial dysfunction is evident in CCHD patients as shown by strikingly reduced endothelial vasodilation to Ach. The response to exogenous ET-1 is reduced, possibly because of elevated endogenous ET-1 levels, but the effects of endogenous ET-1 on arterial tone are not enhanced, as indicated by the similar response to ET-1 blockade.”

Endothelin-1 is a Novel Prognostic Factor in Non-Small Cell Lung Cancer
Mr C. Arun, M. DeCatris, D.M. Hemingway, N.J.M. London, and K.J. O'Byrne
The International Journal of Biological Markers Vol 19, Issue 4, pp. 262 – 267

Study population: patients with non-small lung cancer (NSCLC, n=30), NSCLC cell lines (n=10)
Sample Type: EDTA Plasma, cell supernatent
Conclusions: “. In conclusion, big ET-1/ET-1 is expressed by resected NSCLC specimens and tumour cell lines. Plasma big ET-1 levels are elevated in NSCLC patients compared to controls with levels >7.8 pg/mL being associated with a worse outcome. The development of selective ET-1 antagonists indicates that ET-1 may be a therapeutic target in NSCLC.”

Prognostic significance of elevated endothelin-1 levels in patients with colorectal cancer.
Arun C, London NJ, Hemingway DM.
Int J Biol Markers. 2004 Jan-Mar;19(1):32-7.
PMID: 15077924.

Study population: patients with colorectal cancer (n=65)
Sample Type: Plasma
Conclusions: “Preoperative plasma big ET-1 levels may be useful in predicting overall survival in patients with colorectal cancer. Plasma big ET-1 levels may be useful in the selection of high-risk lymph node-negative patients with colorectal cancer for adjuvant therapy.”

Increased circulating endothelins are not of cardiopulmonary origin in heart failure patients.
Wang YZ, Goetze JP, Videbaek R, Rehfeld JF, Kastrup J.
Scand J Clin Lab Invest. 2005;65(4):341-7.
PMID: 16076689.

Study population: patients with heart failure (n=12), healthy controls (n=12)
Sample Type: Plasma
Conclusions: “In heart failure patients, increased plasma concentrations of endothelin-1 and big-endothelin mainly reflect an increased secretion from the peripheral endothelium.”

Correlations between clinical presentation, brain natriuretic peptide, big endothelin-1, tumor necrosis factor-alpha and cardiac troponins in heart failure patients.
Boffa GM, Zaninotto M, Bacchiega E, Nalli C, Forni M, Tiso E, Cacciavillani L, Razzolini R, Plebani M.
Ital Heart J. 2005 Feb;6(2):125-32.
PMID: 15819505.

Study population: patients with heart failure (n=120)
Sample Type: Plasma
Conclusions: “The plasma concentrations of BNP and BET-1 showed the best and comparable correlations with parameters describing the clinical status of patients with heart failure, in particular with the presence of pulmonary venous congestion. The value of the plasma concentration of TNF-alpha and those of cardiac troponins were found to be limited in patients with relatively stable heart failure.”

Superiority of big endothelin-1 and endothelin-1 over natriuretic peptides in predicting survival in severe congestive heart failure: a 7-year follow-up study. 
Van Beneden R, Gurné O, Selvais PL, Ahn SA, Robert AR, Ketelslegers JM,
Pouleur HG, Rousseau MF. 
J Card Fail. 2004 Dec;10(6):490-5.
PMID: 15599839.

Study population: patients with congestive heart failure (CHF, n=47)
Sample Type: Plasma
Conclusions: “Big ET-1 and ET-1 are strong independent predictors of survival in patients with severe CHF and better for this purpose than natriuretic peptides or their pro-peptides. These markers allow easily to identify a population with a very high risk mortality eligible for more aggressive therapies.”

Val-HeFT Investigators. The comparative prognostic value of plasma neurohormones at baseline in patients with heart failure enrolled in Val-HeFT.
Latini R, Masson S, Anand I, Salio M, Hester A, Judd D, Barlera S, Maggioni AP, Tognoni G, Cohn JN.
Eur Heart J. 2004 Feb;25(4):292-9.
PMID: 14984917.

Study population: patients with heart failure (CHF, n=4300)
Sample Type: Plasma
Conclusions: “All the neurohormones evaluated in 4300 patients with stable moderate to severe HF were found to be significant markers of outcome, despite therapy with ACEi, BB and randomization to an angiotensin receptor blocker or placebo. Several of these markers have been implicated as contributors to progression of HF, but BNP, which is thought to be protective, was the most powerful indicator for poor outcome.”

The endothelin system in Morris hepatoma-7777: an endothelin receptor antagonist inhibits growth in vitro and in vivo.
Pfab T, Stoltenburg-Didinger G, Trautner C, Godes M, Bauer C, Hocher B.
Br J Pharmacol.
2004 Jan;141(2):215-22.
PMID: 14662722

Study population: Morris hepatoma 7777 cells
Sample Type: Cell supernatent
Conclusions: “In conclusion, the endothelin system is activated in Morris hepatoma 7777 and contributes to hepatoma growth. Since endothelin receptor antagonists are well-tolerated upcoming clinically used drugs without major side effects, our data might provide a new pharmacological approach to reduce hepatoma growth in vivo.”

Influence of inhaled iloprost on transpulmonary gradient of big endothelin in patients with pulmonary hypertension.
Wilkens H, Bauer M, Forestier N, König J, Eichler A, Schneider S, Schäfers HJ, Sybrecht GW.
Circulation. 2003 Mar 25;107(11):1509-13.
PMID: 12654608.

Study population: patients with pulmonary hypertension (n=15)
Sample Type: EDTA Plasma
Conclusions: “An increase in pulmonary clearance of big-ET could be a mechanism contributing to the beneficial effects of inhaled prostanoids in the treatment of PAH.”

The role of big endothelin-1 in colorectal cancer.
Arun C, Swift B, Porter KE, West KP, London NJ, Hemingway DM.
Int J Biol Markers. 2002 Oct-Dec;17(4):268-74.
PMID: 12521131.

Study population: Patients who underwent surgery for primary colorectal cancer (n=60) and those with known colorectal liver metastases (n=45), controls (n=20)
Sample Type: EDTA Plasma
Conclusions: “This study has demonstrated elevated concentrations of big ET-1 in colorectal cancer patients, especially in those with hepatic metastases. Upregulation of ET activity in colorectal cancer could be inferred by the increased immunostaining of big ET-1 in cancer cells. Therefore, plasma big ET-1 levels should be evaluated as a potential tumour marker for the identification of hepatic metastases at an earlier stage.”

Blood pressure-independent additive effects of pharmacologic blockade of the renin-angiotensin and endothelin systems on progression in a low-renin model of renal damage. Amann K, Simonaviciene A, Medwedewa T, Koch A, Orth S, Gross ML, Haas C, Kuhlmann A, Linz W, Schölkens B, Ritz E.
J Am Soc Nephrol. 2001 Dec;12(12):2572-84.
PMID: 11729225.

Study population: Nephrectomized (SNX) and sham-operated rats
Sample Type: Plasma
Conclusions: “The results document BP-independent effects of the ACE-i and AT1-RA on the GSI and urinary albumin excretion and an effect of the ET-RA on the GSI. The contrasting results suggest different pathogenetic pathways for glomerulosclerosis and albuminuria. The combination of treatments provided superior effects on the GSI and tubulointerstitial index but not on urinary albumin excretion.”

Endogenously released endothelin-1 from human pulmonary artery smooth muscle promotes cellular proliferation: relevance to pathogenesis of pulmonary hypertension and vascular remodeling.
Wort SJ, Woods M, Warner TD, Evans TW, Mitchell JA.
Am J Respir Cell Mol Biol. 2001 Jul;25(1):104-10.
PMID: 11472982.

Study population: Human pulmonary artery smooth-muscle (HPASM) cells
Sample Type: Cell supernatent
Conclusions: “We conclude that ET-1 released from HPASM cells has an autocrine function in serum-induced proliferation, with important implications for the pathogenesis of human vascular remodeling. Drugs used in the treatment of pulmonary hypertension may act, at least in part, by inhibiting this autocrine loop.”

Better microvascular function on long-term treatment with lisinopril than with nifedipine in renal transplant recipients.
Asberg A, Midtvedt K, Vassbotn T, Hartmann A.
Nephrol Dial Transplant. 2001 Jul;16(7):1465-70.

Study population: Hypertensive renal transplant recipients (n=75)
Sample Type: Plasma
Conclusions: “The study indicates that long-term treatment with lisinopril, when compared with nifedipine, yields a more beneficial effect on microvascular function in hypertensive renal transplant recipients on CsA. The beneficial microvascular effect may be mediated in part by an endothelin-1-associated effect on the endothelium.”

Evaluation of big endothelin-1 concentrations in serum and ventricular cerebrospinal fluid after early surgical compared with nonsurgical management of ruptured intracranial aneurysms.
Gruber A, Roessler K, Georgopoulos A, Missbichler A, Bonelli R, Richling B.
Neurosurg Focus. 2000 May 15;8(5):e6.
PMID: 16859284.

Study population: Patients with severe post-subarachnoid hemorrhage (SAH, n=44)
Sample Type: Serum and CSF
Conclusions: “Among patients with SAH who received treatment during the acute phase, those undergoing early aneurysm surgery were shown to have lower big ET-1 CSF levels than those receiving embolization and no treatment (that is, the nonsurgical treatment groups).”

Physical training improves flow-mediated dilation in patients with the polymetabolic syndrome.
Lavrencic A, Salobir BG, Keber I.
Arterioscler Thromb Vasc Biol. 2000 Feb;20(2):551-5.
PMID: 10671187.

Study population: Men with polymetabolic syndrome (n=30)
Sample Type: Citrate Plasma
Conclusions: “In conclusion, our findings suggest that a 3-month physical training program, which improved maximal exercise capacity, enhances flow-mediated dilation in patients with the polymetabolic syndrome.”

Direct enzyme immunometric measurement of plasma big endothelin-I concentrations and correlation with indicators of left ventricular function.
Haug C, Koenig W, Hoeher M, Kochs M, Hombach V, Gruenert A, Osterhues H.
Clin Chem. 1998 Feb;44(2):239-43.

PMID: 9474018.

Study population: Patients undergoing undergoing cardiac catheterization (n=90)
Sample Type: EDTA Plasma
Conclusions: “Plasma big endothelin-1 concentrations were notably greater in patients with New York Heart Association (NYHA) class II–IV symptoms than in patients without cardiac disease or in patients categorized to NYHA class I. These data suggest that plasma big endothelin-1 concentrations, measured by a direct ELISA, correlate with hemodynamic indicators and symptoms of left ventricular dysfunction.”


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