Expression of endothelin-1 and endothelin-converting enzyme-1 mRNAs and proteins in failing human hearts.
Accumulating evidence suggests that endogenous endothelin-1 (ET-1) may contribute to the development of heart failure. In this study we determined sites of ET-1 synthesis and production in the failing human myocardium by immunohistochemistry and in situ hybridization for ET-1 and endothelin-converting enzyme-1 (ECE-1). Myocardial tissues were obtained from 19 patients with heart failure and from four noncardiac patients as controls. In both failing and nonfailing hearts, apparent immunoreactivity for ET-1 and ECE-1 was consistently seen in cardiac myocytes. Endothelial cells of intramyocardial coronary arteries and veins had only weak or focal ET-1 and apparent ECE-1 immunoreactivities. On the other hand, in situ hybridization showed strong signals for ET-1 and ECE-1 mRNAs in vascular endothelial cells but a lesser intensity of signals in cardiac myocytes. Apparent immunoreactivity and strong hybridization signals for both ET-1 and ECE-1 were seen in macrophages, which were abundant in infarcted regions of ischemic cardiomyopathy and in myocardium of septic patients but were rare in healthy hearts. These results suggest that, in failing human heart, vascular endothelial cells and macrophages rather than cardiac myocytes appear to be the principal ET-1 synthetic sites, although ET-1 peptides are abundantly present in cardiac myocytes of both failing and nonfailing hearts. Endogenous ET-1 may play a pathophysiologic role in human heart failure.
Fukuchi
M
M
Department of Medicine, Montreal General Hospital, Quebec, Canada.
Giaid
A
A
D016282:Aspartic Acid Endopeptidases / Q000096:biosynthesis*; D019332:Endothelin-1 / Q000096:biosynthesis*; D000072396:Endothelin-Converting Enzymes; D006333:Heart Failure / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008666:Metalloendopeptidases; D009124:Muscle Proteins / Q000096:biosynthesis*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis*
D019332:Endothelin-1; D009124:Muscle Proteins; D012333:RNA, Messenger; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; C000606923:ECE1 protein, human; D000072396:Endothelin-Converting Enzymes