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 vascular endothelium and the perspective from which we consider the mechanisms of vascular control. It is now known that the vascular endothelium plays a key role in circulatory homeostasis through its ability to sense the local vascular milieu and respond to it by the synthesis and release of a variety of biologically active substances. The endothelium influences not only vascular tone, but also vascular remodeling via the production of growth-promoting and growth-inhibiting substances; hemostasis and thrombosis through antiplatelet, anticoagulant, and fibrinolytic effects; and inflammation through the expression of chemotactic and adhesion molecules on the cell membrane. In diseases such as atherosclerosis, however, these functions of the endothelium are impaired and may even become counterproductive and disease-promoting. The "activated" or injured endothelial cells paradoxically become prothrombotic, growth-promoting, and leukocyte-adhesive. The endothelium also loses its vasodilating ability, rendering the underlying vascular smooth muscle susceptible to a preponderance of vasoconstrictive forces. It is now recognized that these disturbances in endothelial function are principal players in the ischemic manifestations of coronary artery disease. Endeavors to modify or reverse endothelial dysfunction may 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.