Down-regulation of endothelial expression of endothelial cell protein C receptor and thrombomodulin in coronary atherosclerosis

Coronary atherosclerosis with occlusive thrombosis is the major cause of ac ute myocardial infarction. Although plaque rupture is usually hypothesized to be the predisposing event in coronary thrombosis, the possibility cannot be excluded that local changes in the anticoagulant properties of the endo thelium overlying the plaque contribute to this process. It is evident that thrombomodulin and the endothelial cell protein C receptor are critical pl ayers in the control of the thrombogenic process. This study examined wheth er thrombomodulin and the endothelial cell protein C receptor are down-regu lated on endothelial cells overlying the atherosclerotic plaque in coronary arteries and thus could potentially favor local thrombus formation. Sectio ns of archival left and right coronary arteries (n = 18 each) with severe a therosclerosis from the native heart of six patients who underwent heart tr ansplantation were immunostained for CD31, CD34, endothelial cell protein C receptor, and thrombomodulin using a streptavidin-biotin-peroxidase method . Controls included left and right coronary arteries from autopsy cases wit h no atherosclerosis (n = 6), and also from cases with mild atherosclerosis (n = 5). The apparent density of all of these proteins was much higher in control than in atherosclerotic arteries. Our findings support the hypothes is that both endothelial cell protein C receptor and thrombomodulin are dow n-regulated in coronary arteries with atherosclerosis. These changes would be expected to result in reduced inhibition of thrombogenic and anti-inflam matory activity on the endothelium overlying atherosclerotic regions and th us could contribute to coronary thrombosis.