Endothelial function and coronary artery disease

The endothelium produces a number of vasodilator and vasoconstrictor substa nces that not only regulate vasomotor tone, but also the recruitment and ac tivity of inflammatory cells and the propensity towards thrombosis. Endothe lial vasomotor function is a convenient way to assess these other functions , and is related to the long-term risk of cardiovascular disease. Lipids (p articularly low density lipoprotein cholesterol) and oxidant stress play a major role in impairing these functions, by reducing the bioavailability of nitric oxide and activating proinflammatory signalling pathways such as nu clear factor kappa B. Biomechanical forces on the endothelium, including lo w shear stress from disturbed blood flow, also activate the endothelium inc reasing vasomotor dysfunction and promoting inflammation by upregulating pr o-atherogenic genes. In contrast, normal laminar shear stress promotes the expression of genes that may protect against atherosclerosis. The subcellul ar structure of endothelial cells includes caveolae that play an integral p art in regulating the activity of endothelial nitric oxide synthase. Low de nsity lipoprotein cholesterol and oxidant stress impair caveolae structure and function and adversely affect endothelial function. Lipid-independent p athways of endothelial cell activation are increasingly recognized, and may provide new therapeutic targets. Endothelial vasoconstrictors, such as end othelin, antagonize endothelium-derived vasodilators and contribute to endo thelial dysfunction. Some but not all studies have linked certain genetic p olymorphisms of the nitric oxide synthase enzyme to vascular disease and im paired endothelial function. Such genetic heterogeneity may nonetheless off er new insights into the variability of endothelial function. Curr Opin Lip idol 12:383-389,, (C) 2001 Lippincott Williams & Wilkins.