ROLE OF ENDOTHELIUM IN ISCHEMIC CORONARY SYNDROMES

The recent discovery that the endothelium synthesizes several powerful vasodilators, including prostacyclin and endothelium-derived relaxing factor, has substantially changed our view of the importance of the v ascular endothelium and the perspective from which we consider the mec hanisms of vascular control. It is now known that the vascular endothe lium plays a key role in circulatory homeostasis is through its abilit y to sense the local vascular milieu and respond to it by the synthesi s and release of a variety of biologically active substances. The endo thelium influences not only vascular tone, but also vascular remodelin g via the production of growth-promoting and growth-inhibiting substan ces; hemostasis and thrombosis through antiplatelet, anticoagulant, an d fibrinolytic effects; and inflammation through the expression of che motactic and adhesion molecules on the cell membrane. In diseases such as atherosclerosis, however, these functions of the endothelium are i mpaired and may even become counterproductive and disease-promoting. T he ''activated'' or injured endothelial cells paradoxically become pro thrombotic, growth-promoting and leukocyte-adhesive. The endothelium a lso losses its vasodilating ability, rendering the underlying vascular smooth muscle susceptible to a preponderance of vasoconstrictive forc es. It is now recognized that these disturbances in endothelial functi on are principal players in the ischemic manifestations of coronary ar tery disease. Endeavors to modify or reverse endothelial dysfunction m ay therefore be of significant therapeutic benefit in the treatment of myocardial ischemia. This review outlines several important insights into the biology of the arterial wall that are currently being applied to the study of coronary artery disease in humans.