Endothelial dysfunction in atherosclerosis

Abstract

Endothelial regulation of vasomotor tone occurs largely via the release of nitric oxide or a closely related compound. This process is strikingly altered in a variety of disease states, and alterations of vasomotion may be responsible for the development of hypertension, altered tissue perfusion, and an enhanced propensity for vasoconstriction in several common disorders. In hypercholesterolemia and atherosclerosis, this alteration of vasomotor control occurs not only in larger vessels, but in the microcirculation. Explanations for impaired endothelium-dependent vascular relaxations in hypercholesterolemia include impairments in endothelial cell signal transduction, deficiencies in the substrate (arginine) for the enzyme nitric oxide synthase, alterations in the nitric oxide synthase enzyme or one of its co-factors, and excess destruction of nitric oxide by the superoxide anion. In this review, evidence for these alterations will be considered, potential interventions for restoring endothelium-dependent relaxations examined, and the possible impact of endothelial dysfunction in atherosclerosis considered.