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Clinical significance of endothelin in cardiovascular disease
E L Schiffrin1, H D Intengan, G Thibault
1Clinical Research Institute of Montreal, Quebec, Canada.
Insights
Endothelins, peptides produced by the endothelium, are implicated in cardiovascular diseases like hypertension and heart failure. Endothelin antagonism shows promise as a therapeutic strategy for these conditions.
Area of Science:
- Cardiovascular Physiology and Pathophysiology
- Endocrinology
- Vascular Biology
Background:
- Endothelins are vasoactive peptides produced by endothelial cells.
- Endothelin-1 is the primary endothelin isoform involved in cardiovascular regulation.
- These peptides play significant roles in both normal physiological functions and disease states.
Purpose of the Study:
- To review the multifaceted roles of endothelins in cardiovascular physiology and pathophysiology.
- To explore the involvement of endothelins in various cardiovascular diseases, including hypertension, heart failure, and atherosclerosis.
- To highlight the therapeutic potential of endothelin antagonists and endothelin-converting enzyme inhibitors.
Main Methods:
- Literature review of studies investigating endothelin's role in cardiovascular diseases.
- Analysis of experimental models of hypertension, heart failure, and vascular diseases.
- Examination of clinical data on endothelin's involvement in human cardiovascular conditions.
Main Results:
- Endothelins contribute to vasoconstriction, potentially elevating blood pressure and causing vascular hypertrophy in hypertension models.
- Enhanced endothelin expression is observed in heart failure, atherosclerosis, coronary artery disease, and pulmonary hypertension.
- Endothelin antagonism has demonstrated beneficial effects in experimental models and some human conditions like heart failure and subarachnoid hemorrhage.
Conclusions:
- Endothelins are critically involved in the pathogenesis of numerous cardiovascular diseases.
- Targeting the endothelin pathway with antagonists or enzyme inhibitors presents a promising therapeutic avenue.
- Further research into endothelin's role may uncover new treatment strategies for cardiovascular disorders.
Abstract:
Endothelins are ubiquitously produced 21-amino-acid peptides that were discovered as an endothelial product and may play important roles in cardiovescular physiology and pathophysiology. The main endothelin produced by the endothelium is endothelin-1. The vasoconstrictor role of endothelins may participate in blood pressure elevation and vascular hypertrophy in salt-dependent models of hypertension (deoxycorticosterone acetate-salt hypertensive rats, spontaneously hypertensive rats treated with deoxycorticosterone, acetate and salt, and Dehl salt-sensitive rats), and in stroke-prone spontaneously hypertensive rats. In humans, endothelins may play important roles in moderate to severe essential hypertension, and in the hypertension of African-Americans. Endothelins may be involved in cardiac hypertrophy, and there is increasing evidence of their participation in heart failure, in which acute endothelin antagonism in humans exerts beneficial effects. Endothelin expression is enhanced in smooth muscle cells migrating into the intima of arteries in atherosclerosis, suggesting a role in atherogenesis. Endothelin may participate as a vasoconstrictor in coronary artery disease, and as a contributor to intimal proliferation in restenosis after coronary angioplasty. In patients with myocardial infarction, cardiac production of endothelin is increased, particularly in those with cardiogenic shock. There is a potential for participation of endothelins in vasospasm accompanying stroke or subarachnoid hemorrhage: in the latter, endothelin antagonism has shown beneficial effects in experimental models. In neonatal and in primary pulmonary hypertension, endothelin expression is enhanced, and in experimental models endothelin antagonism resulted in favorable responses. Systemic sclerosis is another, peripheral, form of vascular disease in which endothelin may play a role and in which endothelin antagonism may be an interesting therapeutic alternative. The pathophysiologic role of endothelins is becoming increasingly apparent in cardiovascular disease, generating interesting potential therapeutic targets for the use of endothelin antagonists or endothelin-converting enzyme inhibitors.