Endothelin-like immunoreactivity in atherosclerotic human coronary arteries

Endothelin-1 (ET-1) is an endothelium-derived peptide with powerful vasoconstrictor and mitogenic properties. A pathophysiologic role for ET-1 has been suggested, because increased plasma and tissue levels of this peptide have been described in a number of disease states, including atherosclerosis. Immunocytochemistry was carried out on sections of coronary arteries from patients undergoing cardiac transplantation to identify regions exhibiting ET-1-like immunoreactivity (ET-LI). ET-LI was associated with endothelial cells of the lumen and with microvascular endothelial cells of the adventitia, regions of neovascularization, and recanalization within atherosclerotic plaques. ET-LI was observed in the tunica media, and patches of immunostaining were also associated with smooth-muscle cells within the plaque. These results indicate that ET-1 not only is released from the vascular endothelium but, under certain conditions, is also generated by smooth muscle cells. An autocrine action of ET-1 is well established, and our results suggest that this peptide is involved in neovascularization and smooth-muscle cell proliferation associated with atherosclerosis.