1012-105 Endothelin Immunoreactivity in Human Coronary Atherosclerosis

Abstract

Coronary atherosclerosis and restenosis are disease processes involving cell proliferation and activation of growth factors. Endothelin-l (ET-l), a vasoconstrictor and mitogenic peptide, is produced from its precursor Big-ET. Coronary plasma ET concentrations are elevated in coronary atherosclerosis and following coronary interventions. The current study was designed to test the hypothesis that ET is produced and present in human coronary atherosclerotic and restenotic lesions and localized to both endothelial and nonendothelial cells. Twenty coronary lesions were obtained utilizing directional atherectomy. Immunohistochemistry for endothelins was performed with rabbit polyclonal ET-l and Big-ET antiserum without cross reactivity between Big-ET and ET-1 antisera. In addition, staining for specific cell types, including macrophages (KP-1), endothelial cells (Factor VIII), and myointimal cells (actin), was performed. Eight primary native lesions, six restenotic lesions, and six vein graft (VG) lesions were studied. In all lesion types, intracellular Big-ET and ET-1 were present and in the extracellular matrix and colocalized to area with endothelial cells, macrophages, fibroblasts, and myointimal cells. ET-1 and Big-ET were colocalized to area with myointimal cells only in the primary native lesions. This study demonstrates the presence of Big-ET and ET-1 in coronary and VG atherosclerotic and restenotic lesions. This study suggests that ET is produced locally in the atherosclerotic and restenotic lesions by endothelial and nonendothelial cells. ET may playa role in the changes in tissue architecture and pathogenesis of coronary and VG atherosclerosis and restenosis.