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Big ENDOTHELIN-1 a prognostic marker in CAD.  Endothelin-1 (ET-1) is the most potent vasoconstrictor peptide. This 21 amino acid peptide is the biologically active from that is rapidly cleared from the circulation. Its low concentrations and short half-life make it challenging to detect in serum and plasma samples. Big-Endothelin-1 (BigET-1) is the precursor peptide in the synthesis of Endothelin-1 (ET-1).  It circulates in higher concentrations  and also has a much longer half-life than ET-1. Therefore, measurement of plasma BigET-1 levels are an alternative approach for the indirect estimation of ET-1 release (1).

BigET-1 is primarily produced by endothelial cells and is produced through cleavage of “preproendothelin”, a larger precurser protein. The conversion of BigET-1 to the biologically active 21 amino acid ET-1, is a result the proteolytic cleavage by endothelin-converting enzymes (ECEs) (2). Big-ET-1 has been reported as an independent predictor of cardiovascular mortality in patients with chronic heart failure as determined in a large cohort study in more than 2800 individuals (3). In addition, Big ET-1 has been shown to be a strong and independent predictor of mortality in patients with moderate to severe light chain cardiac amyloidosis (AL-CA) , which may indicate a possible role for risk stratification in patients with this disease (4).

Big ENDOTHELIN-1 can easily be measured in serum and plasma samples.

Biomedica Big Endothelin ELISA Assay 

 

Download your protocol booklet  here

Big ENDOTHELIN-1 a prognostic marker in CAD

The Biomedica BigET-1 ELISA assay was highlighted in this large cohort study of nearly 8000 prediabetic and diabetic patients with stable Coronary Artery Disease (CAD): Prognostic Value of Plasma Endothelin-1 in Predicting Worse Outcomes in Patients with Prediabetes and Diabetes and Stable Coronary Artery Diseases. Yang C et al., Diabetes Metab J. 2024. 

Key findings

  • Plasma BigET-1 level is an independent predictor of #cardiovascular events (CVEs) in patients with stable CAD. 
  • BigET-1 remains independently associated with worse cardiovascular outcomes in prediabetic and diabetic patients but not in patients with normoglycemia.
  • Patients with diabetes and high BigET-1 levels were associated with the highest risk of CVEs in patients with stable CAD.
  • Targeting ET-1 pathways may help manage CAD in individuals with dysglycemia.

 

Literature

  1. Biomarkers and Precision Medicine in Heart Failure . Nasrien E. Ibrahim et al., Heart Failure: a Companion to Braunwald’s Heart Disease (Fourth Edition), 2020.
  2. Endothelin-1 levels and cardiovascular events. Jankowich M, Choudhary G. Trends Cardiovasc Med. 2020 Jan;30(1):1-8. doi: 10.1016/j.tcm.2019.01.007.PMID: 30765295.
  3. 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; 22(3-4):315-320. doi: 10.1080/1354750X.2016.1252969. PMID: 27788598.
  4. Prognostic value of plasma big endothelin-1 in patients with light chain cardiac amyloidosis. Chen Z, Shi A, Wang Z, Chen Y, Lin Y, Su M, Dong H, Laptseva N, Hu Y, Flammer AJ, Duru F, Jin W, Chen L. Heart. 2024; 26;110(18):1124-1132. doi: 10.1136/heartjnl-2024-324000. PMID: 39084705.
  5. Prognostic Value of Plasma Endothelin-1 in Predicting Worse Outcomes in Patients with Prediabetes and Diabetes and Stable Coronary Artery Diseases. Yang C, Zhu CG, Guo YL, Wu NQ, Dong Q, Xu RX, Wu YJ, Qian J, Li JJ. Diabetes Metab J. 2024 Sep;48(5):993-1002. doi: 10.4093/dmj.2023.0410. Epub 2024 Aug 21. PMID: 39165112.

 

Further reading

 

November is Diabetes Awareness Month bringing attention to diabetes and its impact on millions of individuals.

Diabetes mellitus has emerged as the third most significant non-communicable disease, following cardiovascular diseases and cancer. This condition encompasses a group of metabolic disorders marked by chronic hyperglycemia resulting from various causes, along with inadequate insulin secretion and impaired insulin action. According to the most recent statistics from the International Diabetes Federation, the global number of individuals with diabetes reached 530 million in 2021, with projections suggesting it could exceed 780 million by 2045. Due to the long-term nature of the disease, diabetes can lead to damage across multiple body systems or organs, resulting in various complications (1, 2). Beyond the more commonly known complications of diabetes such as heart disease, diabetes can also affect the skeletal system. This severe complication of diabetes leads to bone loss potentially resulting in osteoporosis and increased fracture risk.

Identifying biomarkers that may predict fracture risk in individuals with diabetes is crucial for improving patient care.

Sclerostin and Fracture Risk Prediction in Diabetes

Sclerostin (SOST) is a bone-related protein that is mainly produced by osteocytes, bone cells embedded in the bone matrix. Sclerostin is considered to be one of the major regulators of bone formation. It is a soluble antagonist of the Wnt signaling pathway and its inactivation leads to bone degradation, while the  of Wnt signaling promotes bone formation (3). Sclerostin has been a target of therapeutic antibodies for osteoporosis treatment due to its role in inhibiting bone formation.

Bone as an endocrine organ

Research indicates that bone, which is involved in lipid and glucose metabolism, is increasingly recognized as an endocrine organ. Recent findings suggest that sclerostin contributes to disorders related to lipid and glucose metabolism (4). Studies have shown that Sclerostin levels are increased in individuals with prediabetes and correlated with insulin resistance in the skeletal muscle, liver, and adipose tissue (5). In addition, Sclerostin levels have been shown to be negatively associated with insulin sensitivity in obese but not in lead woman (6).

Further studies have revealed that increased serum Sclerostin levels are associated with vertebral fractures in patients with type 2 diabetes mellitus (7, 8). Sclerostin, has also been suggested to have predictive value for fracture risk in patients with diabetes (9).

Sclerostin – a promising circulating marker of diabetic bone disease

Sclerostin has emerged as a promising circulating marker of diabetic bone disease. It may not only reflect the degree of osteocyte dysfunction and the suppression of bone formation that occurs in this disease, but it may also potentially reflect the vascular alterations that are associated with specific bone alterations such as cortical porosity (10).

Additional research is essential to enhance the understanding of biochemical markers in the assessment of diabetic bone disease. Specifically, the ability of bone markers to forecast fracture risk needs further examination.

Circulating Sclerostin levels can reliably be measured in human serum and plasma samples with a conventional SCLEROSTIN ELISA Assay Kit.

Sclerostin ELISA (cat. no. BI-20492)

  • MOST referenced in more than 300 citations
  • LOW sample volume – 20µl sample /well
  • For SERUM & PLASMA samples
  • RELIABLE – full validation package

 

Bioactive Sclerostin ELISA (cat. no. BI-20472)

  • CHARACTERIZED ANTIBODIES – targeting the receptor binding region
  • RIGOROUSLY validated for clinical samples
  • LOW sample volume – 20µl sample /well
  • RELIABLE – full validation package

 

Literature

  1. International Diabetes Federation – Facts and Figures
  2. Diabetes mellitus, the fastest growing global public health concern: Early detection should be focused. Hossain MJ, Al-Mamun M, Islam MR. Health Sci Rep. 2024; 7(3):e2004. doi: 10.1002/hsr2.2004. PMID: 38524769.
  3. Role of Wnt signaling and sclerostin in bone and as therapeutic targets in skeletal disorders. Marini F, Giusti F, Palmini G, Brandi ML. Osteoporos Int. 2023; 34(2):213-238. doi: 10.1007/s00198-022-06523-7. PMID: 35982318.
  4. The role of sclerostin in lipid and glucose metabolism disorders. Jiang H, Li D, Han Y, Li N, Tao X, et al., Biochem Pharmacol. 2023; 215:115694. doi: 10.1016/j.bcp.2023.115694. PMID: 37481136.
  5. Sclerostin and Insulin Resistance in Prediabetes: Evidence of a Cross Talk Between Bone and Glucose Metabolism. Daniele G, Winnier D, Mari A, Bruder J, Fourcaudot M, Pengou Z, Tripathy D, Jenkinson C, Folli F. Diabetes Care. 2015; 38(8):1509-17. doi: 10.2337/dc14-2989. PMID: 26084344.
  6. Serum sclerostin is negatively associated with insulin sensitivity in obese but not lean women. Aznou A, Meijer R, van Raalte D, den Heijer M, Heijboer A, de Jongh R. Endocr Connect. 2021; 10(2):131-138. doi: 10.1530/EC-20-0535. PMID: 33480863.
  7. Increased serum sclerostin and decreased serum IGF-1 are associated with vertebral fractures among postmenopausal women with type-2 diabetes. M.S. Ardawi, D.H. Akhbar, A. Alshaikh, M.M. Ahmed, M.H. Qari, A.A. Rouzi, et al. Bone, 56 (2013), pp. 355-362
  8. Elevated sclerostin levels are associated with vertebral fractures in patients with type 2 diabetes mellitus. Yamamoto M, Yamauchi M, Sugimoto T. J Clin Endocrinol Metab. 2013; 98(10):4030-7. doi: 10.1210/jc.2013-2143. PMID: 23894157.
  9. Fracture risk assessment in diabetes mellitus. Front Endocrinol (Lausanne). Chen W, Mao M, Fang J, Xie Y, Rui Y. 2022; 13:961761. doi: 10.3389/fendo.2022.961761. PMID: 36120431.
  10. Biochemical Markers of Bone Fragility in Patients with Diabetes. A Narrative Review by the IOF and the ECTS. Meier C, Eastell R, Pierroz DD, Lane NE, Al-Daghri N, Suzuki A, Napoli N, Mithal A, Chakhtoura M, El-Hajj Fuleihan G, Ferrari S. J Clin Endocrinol Metab. 2023; 108(10):e923–36. doi: 10.1210/clinem/dgad255. PMID: 37155585.