The endothelium, platelets, and coronary vasospasm

Significant advances have been made in our understanding of the role of the vascular endothelium in preventing thrombosis and in decreasing vascular spasm. The endothelium provides a surface receptor, thrombomodulin, that binds thrombin. In this form, thrombin loses its ability to clot fibrinogen or to aggregate platelets, but is able to activate protein C. In its activated state, protein C is able to act as an inhibitor of coagulation by virtue of its proteolytic destruction of Factors Va and VIIIa. Congenital deficiency of protein C is associated with early and recurrent thrombosis. The discovery that the endothelium is responsible for the production of a short-acting inhibitor of smooth-muscle contraction (EDRF) was a remarkable advance. One of the EDRF substances has been demonstrated to be NO, which has inhibitory effects on both smooth muscle and blood platelets. Activity of EDRF appears to be diminished or lost as a consequence of atherosclerosis, and stimuli that cause vasodilation via the EDRF pathway in normal vessels cause vasoconstriction in atherosclerotic arteries. Regression of atherosclerosis in experimental animals appears to be associated with restoration of EDRF activity.