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Role of endothelial dysfunction in atherosclerosis Davignon J; Ganz PCirculation 2004[Jun]; 109 (23 Suppl 1): III27-32As the major regulator of vascular homeostasis, the endothelium exerts a number of vasoprotective effects, such as vasodilation, suppression of smooth muscle cell growth, and inhibition of inflammatory responses. Many of these effects are largely mediated by nitric oxide, the most potent endogenous vasodilator. Nitric oxide opposes the effects of endothelium-derived vasoconstrictors and inhibits oxidation of low-density lipoprotein. A defect in the production or activity of nitric oxide leads to endothelial dysfunction, signaled by impaired endothelium-dependent vasodilation. Accumulating evidence suggests that endothelial dysfunction is an early marker for atherosclerosis and can be detected before structural changes to the vessel wall are apparent on angiography or ultrasound. Many of the risk factors that predispose to atherosclerosis can also cause endothelial dysfunction, and the presence of multiple risk factors has been found to predict endothelial dysfunction. A number of clinical trials have shown that 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) improve endothelial dysfunction in patients with coronary risk factors beyond what could be attributed to their impact on plasma lipids. Studies have elucidated several possible mechanisms by which statin therapy may improve endothelial dysfunction, including upregulation of nitric oxide production or activity and reduction of oxidative stress.|Arteriosclerosis/*physiopathology[MESH]|Coronary Disease/diagnosis/epidemiology/prevention & control/therapy[MESH]|Endothelium, Vascular/diagnostic imaging/*physiopathology[MESH]|Humans[MESH]|Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology/therapeutic use[MESH]|Lipoproteins, LDL/blood[MESH]|Nitric Oxide Synthase Type III[MESH]|Nitric Oxide Synthase/metabolism[MESH]|Nitric Oxide/physiology[MESH]|Oxidative Stress[MESH]|Risk Factors[MESH]|Signal Transduction[MESH]|Treatment Outcome[MESH]|Ultrasonography[MESH]|Vasoconstriction[MESH] |
