Big ENDOTHELIN-1 a prognostic marker in CAD

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 

• EASY – can be used in every lab
• ROBUST & fully VALIDATED (following international quality guidelines)
• HIGHLY SENSTIVE – 0.02 pmol/l (= 0.086 pg/ml)
• GOOD ANALYTE STABILITY in serum and plasma

 

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

• 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, et al., Rev Esp Cardiol. 2005 Mar;58(3):278-84. Spanish. PMID: 15766450.

• Endothelin: 30 Years From Discovery to Therapy. Barton M, Yanagisawa M. Hypertension. 2019; 74(6):1232-1265.