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(Circulation. 2004;109:III-27 – III-32.)
© 2004 American Heart Association, Inc.

Atherosclerosis: Evolving Vascular Biology and Clinical Implications

Role of Endothelial Dysfunction in Atherosclerosis

Jean Davignon, MD; Peter Ganz, MD

From the Hyperlipidemia and Atherosclerosis Research Group/Groupe de recherche sur les hyperlipidémies et l’athérosclérose, Clinical Research Institute of Montreal/Institut de recherches cliniques de Montréal (IRCM) (J.D.), Montreal, Canada; and the Cardiovascular Division (P.G.), Brigham and Women’s Hospital, Boston, Mass.

Correspondence to Jean Davignon, Director of the Hyperlipidemia and Atherosclerosis Research Group, Clinical Research Institute of Montreal (IRCM), 110 Pine Ave W, Montreal, QC H2W 1R7, CANADA. E-mail davignj{at}ircm.qc.ca

As 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.

Key Words: atherosclerosis • endothelial dysfunction • nitric oxide • statins