Increased immunoreactivity of endothelin-1 and endothelin B receptor in human atherosclerotic lesions. A possible role in atherogenesis

This study was designed to analyze the distribution and localization of endothelin-1 (ET-1) and ET receptors (ETA and ETB) at different stages of human atherosclerotic lesions by immunohistochemistry. Compared with ETA receptors, there was increased immunoreactivity of ET-1 and ETB receptor in both unfoamy and foamy macrophages and T lymphocytes in fatty streak and fibrous plaque lesions. In addition, medial SMCs located just beneath the foam cell lesions revealed a higher intensity of ETB receptor immunoreactivity than those located beneath the normal-looking intima without foam cells. In fibrous plaques, intimal SMCs near foam cells showed an increased density of ET receptors with predominant ETB immunoreactivity. In the areas where SMCs showed ETB receptor, ET-1 immunoreactivity was also enhanced. These results suggest that accumulation of foamy macrophages and T lymphocytes may modulate the switching of ET receptor subtypes from ETA to ETB in vascular SMCs, and that the enhanced ET system mediated by ETB receptors may play active roles in the progression of atherosclerosis. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.