Endothelial dysfunction and coronary artery disease.

Abstract

For several decades, the vascular endothelium was considered a unicellular layer acting as a semipermeable membrane between the blood and the interstitium. Recently, it has been demonstrated that the endothelium performs a large range of important biological functions, participating in several metabolic and regulatory pathways. Along with long-known specialized functions like gaseous exchange in the pulmonary circulation and phagocytosis in the hepatic and splenic circulation, the vascular endothelium performs universal roles in the circulation that include participation in thrombosis and thrombolytic control, vascular growth, platelet and leukocyte interactions with the vascular wall, and vasomotor tone. The study of endothelium-dependent vasomotor reactivity has produced over the years, scientific evidence fundamental for the understanding of the endothelium’s role in physiological and pathological situations. In 1977, Moncada et al, published the first report indicating that the endothelium plays a central role in the control of vascular tone via the production of vasoactive substances . In 1980, Furchgott and Zawadzki 2 demonstrated in an experimental preparation of the rabbit aorta, the obligatory role played by endothelial cells in vascular relaxation in response to effectors like acetylcholine, and postulated the existence of a vascular relaxing factor derived from the endothelium. In 1987, two research groups, lead by Ignarro et al , and by Palmer et al , demonstrated that the relaxing factor derived from the endothelium was nitric oxide, an odorless gas until then considered as a mere pollutant. Endothelial dysfunction was first characterized in humans in 1986 by Ludmer et al, 5 who demonstrated that atherosclerotic coronary arteries contracted in response to intracoronary infusion of acetylcholine, while normal coronaries showed dilatation. In 1992, endothelial dysfunction was documented by Celermajer et al 6 in children and otherwise healthy young adults with risk factors for atherosclerosis. Under physiological conditions, the endothelium keeps a reduced vasomotor tone, prevents leukocyte and platelet adhesion, and inhibits the proliferation of vascular smooth muscle cells. In contrast, endothelial dysfunction appears to play a pathogenic role in the initial development of atherosclerosis 7-9 and of unstable coronary syndromes , being associated with atherosclerotic disease risk factors , and being present even before vascular involvement becomes evident . Recent clinical studies have demonstrated that some drugs well known to reduce the incidence of cardiovascular events, improve endothelial function . On the other hand, clinical interventions like the continuous administration of organic nitrates and percutaneous coronary interventions may be associated with adverse effects on the vascular endothelium. In the present article, we will discuss vascular endothelial function versus dysfunction, and their impact on cardiovascular disease, in particular atherosclerosis.