Endothelium dysfunction in the coronary circulation.

Abstract

Coronary artery disease is the most important cause of morbidity and mortality in Western countries. Its pathogenesis is unknown but involves an enhanced vasoconstriction and increased interaction of platelets and monocytes with the vessel wall, as well as proliferation, migration, and extracellular matrix formation of vascular smooth-muscle cells. The endothelium lies in a strategic anatomical position between the circulating blood and vascular smooth-muscle cells. This supports the concept that dysfunction of these cells plays a crucial role in the pathogenesis of coronary artery disease. Endothelial cells are a source of vasodilators such as nitric oxide, prostacyclin, and hyperpolarizing factor. In addition, the cells produce heparin-like substances as well as other molecules with antiproliferative properties. These effects of endothelial cells may explain why platelets and monocytes usually do not adhere at the blood vessel wall and why vascular smooth-muscle cells remain in a vasodilated state and neither migrate nor proliferate. However, under pathological conditions, in particular in the presence of cardiovascular risk factors, endothelial dysfunction occurs and significantly contributes to the increase of platelet-vessel wall interaction, vasoconstriction, and proliferation in the coronary system. Under these conditions, endothelium-dependent vasodilation is reduced and endothelium-dependent constrictor responses are augmented. Furthermore, endothelial cells are also able to produce growth promoters. Hence, endothelial cells are important targets and mediators of coronary artery disease. Therapeutic strategies aimed at improving or preserving endothelial function therefore may be promising in the prevention and treatment of coronary artery disease.