The role of the endothelin system in myocardial infarction—new therapeutic targets?

See doi:10.1016/S1095-668X(02)00420-7for the article to which this editorial refers. Endothelin (ET)-1, a 21-amino acid peptide, represents the major isoform of the endothelin peptide family, which further includes ET-2, ET-3, and ET-4.1 It is the most potent vasoconstrictor known and stimulates cell proliferation in various tissues. The biologically inactive precursor big ET is converted to the mature peptide by the endothelin-converting-enzyme. ETAreceptors, which lead to increased intracellular calcium concentrations, induce vasoconstriction and cell proliferation. ETBreceptors which mediate the release of NO and prostacyclin cause vasodilatation and are involved in the clearance of ET-1 and in the inhibition of the endothelin-converting-enzyme. In atherosclerosis, the production of ET-1 is stimulated and both tissue and plasma ET-1 levels are positively correlated with the extent of atherosclerosis.1 Moreover, in patients with coronaryartery disease, tissue ET-1 levels are related to the extent of angina. Various risk factors for atherosclerosis such as diabetes mellitus, smoking and hypercholesterolaemia enhance endothelial ET-1 secretion.2,3 Oxidized LDL stimulates the production of ET-1 in human macrophages and endothelial cells.4 It is suggested that arterial hypertension is associated with elevated tissue ET-1 levels and/or with altered sensitivity to endogenous ET-1. ET-1 acts as the natural counterpart of nitric oxide (NO), which exerts vasodilating, antithrombotic and antiproliferative effects. The increased release of ET-1 mediates vasoconstriction and smooth muscle cell proliferation via ETAreceptors, acts as chemoattractant for circulating monocytes and induces neutrophil adhesion, platelet aggregation andadhesion molecule expression.1,5 Thereby, ET-1 is involved in atherogenesis and promotes lesion growth and coronary thrombosis. In fact, chronic ETAreceptor blockade …