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Clinical Medicine & Research
Volume 4, Number 1 : 53 -65
doi:10.3121/cmr.4.1.53
© 2006 Marshfield Clinic
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Review

Recent Advances in Understanding Endothelial Dysfunction in Atherosclerosis

Zhihong Yang, MD and Xiu-Fen Ming, MD, PhD

Zhihong Yang, MD, Department of Medicine, Division of Physiology, University of Fribourg, Rue du Musée 5, CH-1700 Fribourg, Switzerland
Xiu-Fen Ming, MD, PhD, Department of Medicine, Division of Physiology, University of Fribourg, Rue du Musée 5, CH-1700 Fribourg, Switzerland

Reprint Requests: Prof. Zhihong Yang, MD, Vascular Biology Laboratory, Department of Medicine, Division of Physiology, University of Fribourg, Rue du Musée 5, CH-1700 Fribourg, Switzerland, Tel: 41-26-300 85 93; Fax: 41-26-300 96 36; Email: zhihong.yang{at}unifr.ch

Over the last two decades, it has become evident that decreased bioavailability of endothelial nitric oxide (NO) produced from endothelial NO synthase (eNOS), referred to as endothelial dysfunction, plays a crucial role in the development and progression of atherosclerosis. Much progress has been made in understanding the mechanisms of decreased endothelial NO bioavailability at the levels of regulation of eNOS gene expression, eNOS enzymatic activity and NO inactivation. Initial studies suggest that increasing eNOS gene expression would improve endothelial NO release in the hope of inhibiting the progression of atherosclerosis. Recent experimental studies, however, do not always support this therapeutic concept and show some evidence that overexpression of eNOS in atherosclerosis may be even harmful for the disease progression.Thus, recent research to improve endothelial function in atherosclerosis has focused on regulation of eNOS enzymatic activity and prevention of NO inactivation by oxidative stress. Since the role of oxidative stress in endothelial NO bioavailability has been reviewed in a large number of comprehensive articles, this article focuses on the relevant regulatory mechanisms of eNOS enzymatic activity that are emerging to play a role in endothelial dysfunction in atherosclerosis.


Key Words: Arginase • Atherosclerosis • BH4 • eNOS • L-arginine • Oxidative stress




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