(Hellenic Journal of Cardiology) HJC ñ 161 Hellenic J Cardiol 48: 161-164, 2007 I t is well known that neurohormonal changes play an important role in the evolution of an acute myocardial in- farction (AMI). 1,2 They are mainly generat- ed in response to myocardial damage in or- der to maintain the patient’s haemodynam- ic stability. Endothelin-1 (ET-1) is one of the major endogenous substances involved in the pathogenesis and evolution of a my- ocardial infarction. There is also evidence suggesting that ET-1 is an important prog- nostic marker in patients with AMI. 1,2 ET-1 is a 21-amino acid peptide and re- presents the major isoform of the endothe- lin peptide family, 1,2 which also includes ET-2, ET-3 and ET-4. The endothelin pe- ptides are produced by endothelial and smooth muscle cells, neural, renal, pul- monary and inflammatory cells. ET-1 is the most potent vasoconstrictor known. The in- active precursor is converted into its active form by ET converting enzyme. ET-1 acts through two receptors, ET-A and ET-B. ET-A receptors lead to increased intracel- lular calcium concentrations and induce vasoconstriction and cell proliferation. ET- B receptors mediate the release of nitric ox- ide and prostacyclin and therefore cause va- sodilatation. They are also involved in the clearance of ET-1 and inhibit the action of ET converting enzyme. 1-3 ET-1 has also been found to play an im- portant role in the pathogenesis of hyper- tension, congestive heart failure and regula- tion of renal function. 3 In the current re- view, we will focus on the role of ET-1 in the pathogenesis and evolution of AMI. The pathogenetic role of ET-1 The effects of ET-1 on the heart are multi- ple. 1,2,4 Normal ET-1 plasma levels produce a positive inotropic effect through an in- crease in intracellular calcium, whereas ele- vated plasma levels of ET-1 result in a de- cline in cardiac output. This is because ET- 1 has a predominantly vasoconstrictive ef- fect, at both peripheral and coronary level, thus resulting in increased afterload and re- duced myocardial perfusion. ET antago- nists have an adverse effect on myocardial contractility in healthy individuals with nor- mal ET-1 plasma levels but improve con- tractility in patients with advanced ventricu- lar dysfunction. 1,4 The regulation of ET-1 synthesis is a complex process that occurs mainly at the mRNA level. 5 The factors that modulate its expression act by increasing or decreasing levels of ET-1 mRNA. 6 Expression of the ET-1 gene in endothelial cells is regulated by numerous factors, including but proba- bly not limited to thrombin, transforming growth factor-‚, shear stress, tumour ne- crosis factor-·, interleukin-1, insulin, an- giotensin II, nitric oxide and hypoxia. 7 There is evidence suggesting that ET- 1 contributes to the process of atheroscle- rosis. 2 ET-1 levels are positively correlated with the extent of atherosclerosis. Other Significance of Endothelin-1 in Myocardial Infarction ATHANASSIOS ANTONOPOULOS, CONSTANDINOS KYRIACOU, GEORGE KAZIANIS Cardiology Dept., 7th IKA Hospital, Athens, Greece Manuscript received: January 11, 2007; Accepted: March 27, 2007. Address: Athanassios Antonopoulos 59 Alexandras Ave. 11474 Athens, Greece e-mail: athandon2000@yahoo.gr Key words: Endothelin-1, myocardial infarction, reperfusion therapy. Review Article Review Article