Role of endothelin-1 in genesis of coronary artery disease.

ABSTRACT

BACKGROUND: The endothelial cells produce the most potent vasoconstrictor known as endothelin-1. Elevated plasma levels of endothelin have been associated with coronary artery disease, essential hypertension and heart failure. The aims of the present study were, to compare the plasma endothelin-1 levels in coronary artery disease patients and healthy controls, to confirm endothelin-1 as surrogate marker for coronary artery disease and to compare the presence of endothelin-1 like immunoreactivity in aortic and internal mammary artery specimens obtained during coronary artery bypass graft surgery. METHODS AND RESULTS: The circulating levels of endothelin-1 were determined by enzyme-linked immunoassay in patients of coronary artery disease (n=145) and compared with healthy controls (n=70). Tissue endothelin-1 immunoreactivity was examined by immunohistochemical method in aortic and internal mammary artery tissue specimens obtained from 20 patients of coronary artery disease during coronary artery bypass grafting to understand the role of endothelin in atherosclerosis. Significantly higher levels (p < 0.001) of endothelin-1 were observed in all patients of coronary artery disease as compared to healthy controls. The immunoreactivity of endothelin-1 was localized to endothelial cell layer in internal mammary artery whereas in aortic specimens, in addition to endothelial cell layer, immunoreactivity was seen in the cytoplasm of smooth muscle cells of intima and media. CONCLUSIONS: The significant increase in plasma endothelin-1 in coronary artery disease cases as compared to healthy subjects and presence of tissue endothelin-1 immunoreactivity in smooth muscle cells of intimal as well as medial layers of aorta confirms the role of endothelin-1 as a surrogate marker of atherosclerosis.