Endothelins in cardiovascular biology and therapeutics

Cardiovascular disease is a major contributor to global morbidity and mortality and is the common end point of many chronic diseases. The endothelins comprise three structurally similar peptides of 21 amino acids in length. Endothelin 1 (ET-1) and ET-2 activate two G protein-coupled receptors - endo...

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Bibliographic Details
Published in:Nature reviews cardiology Vol. 16; no. 8; pp. 491 - 502
Main Authors: Dhaun, Neeraj, Webb, David J
Format: Journal Article
Language:English
Published: England Nature Publishing Group 01.08.2019
Subjects:
Angiogenesis Inhibitors - therapeutic use
Animals
Biological Products - therapeutic use
Cardiovascular Agents - therapeutic use
Cardiovascular disease
Cardiovascular Diseases - drug therapy
Cardiovascular Diseases - physiopathology
Cardiovascular System - physiopathology
Chronic illnesses
Endothelins - physiology
Humans
Kidney diseases
Pulmonary hypertension
ISSN:1759-5002, 1759-5010, 1759-5010
Online Access:Get full text
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Summary:Cardiovascular disease is a major contributor to global morbidity and mortality and is the common end point of many chronic diseases. The endothelins comprise three structurally similar peptides of 21 amino acids in length. Endothelin 1 (ET-1) and ET-2 activate two G protein-coupled receptors - endothelin receptor type A (ET ) and endothelin receptor type B (ET ) - with equal affinity, whereas ET-3 has a lower affinity for ET . ET-1 is the most potent vasoconstrictor in the human cardiovascular system and has remarkably long-lasting actions. ET-1 contributes to vasoconstriction, vascular and cardiac hypertrophy, inflammation, and to the development and progression of cardiovascular disease. Endothelin receptor antagonists have revolutionized the treatment of pulmonary arterial hypertension. Clinical trials continue to explore new applications of endothelin receptor antagonists, particularly in treatment-resistant hypertension, chronic kidney disease and patients receiving antiangiogenic therapies. Translational studies have identified important roles for the endothelin isoforms and new therapeutic targets during development, in fluid-electrolyte homeostasis, and in cardiovascular and neuronal function. Novel pharmacological strategies are emerging in the form of small-molecule epigenetic modulators, biologics (such as monoclonal antibodies for ET ) and possibly signalling pathway-biased agonists and antagonists.
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ISSN:1759-5002
1759-5010
1759-5010
DOI:10.1038/s41569-019-0176-3