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(Circulation. 1996;93:1069-1072.)
© 1996 American Heart Association, Inc.

Articles

Myocardial Endothelin

Does It Play a Role in Myocardial Failure?

Wilson S. Colucci, MD

From the Cardiomyopathy Program and Cardiovascular Divisions, Boston VA Medical Center and Boston University Medical Center, Boston University School of Medicine, Boston, Mass.

Correspondence to Wilson S. Colucci, MD, Cardiomyopathy Program, Boston University Medical Center, 88 E Newton St, Boston, MA 02118.

Key Words: hypertrophy • myocardium • heart failure • endothelin

	Introduction

 
Endothelin (ET) is a 21–amino acid peptide that was initially identified in 1988 by Yanagisawa and colleagues¹ as a potent vasoconstrictor substance elaborated by vascular endothelial cells. Several additional features have since become apparent. First, ET is a multifunctional peptide. In addition to causing contraction of arterial and venous smooth muscle, ET exerts pleiotropic effects on numerous aspects of cardiovascular, neuroendocrine, renal, gastrointestinal, and pulmonary function. Second, although endothelial cells are its major source, ET can be synthesized by numerous other cell types including cardiac myocytes, vascular smooth muscle cells, renal tubular epithelial cells, glomerular mesangial cells, glial cells, macrophages, mast cells, and pituitary cells. Third, ET has diverse effects on gene expression, indicating that in addition to its immediate effects on cellular function, ET may exert long-term effects on cellular growth and phenotype.

ET is synthesized as an approximately 200–amino acid prepro-hormone. Posttranslational cleavage yields a 38– to 39–amino acid pro-ET that undergoes an additional cleavage between Trp²¹-Val²² to yield mature ET. The later cleavage is mediated by one or more "ET converting enzymes," one of which appears to be a metal-dependent neutral endopeptidase. Three isoforms of ET, termed ET-1, ET-2, and ET-3, have been identified, cloned, and sequenced. Two receptors for ET, termed ET_A and ET_B, also have been identified and shown to be expressed on several cardiovascular cell types including endothelial cells, vascular smooth muscle cells, cardiac myocytes, and fibroblasts.² The receptor subtypes bind ET isoforms with different affinities: The ET_A subtype selectively binds ET-1=ET-2>ET-3, . . . [Full Text of this Article]

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