Role of Asymmetric Dimethylarginine (ADMA) in Diabetic Vascular Complications

Authors: Yamagishi, Sho-ichi; Ueda, Seiji; Nakamura, Kazuo; Matsui, Takanori; Okuda, Seiya

Source: Current Pharmaceutical Design, Volume 14, Number 25, September 2008 , pp. 2613-2618(6)

Publisher: Bentham Science Publishers

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Abstract:

Nitric oxide (NO) is a well-recognized anti-atherogenic factor; it inhibits the inflammatory-proliferative processes in atherosclerosis. Indeed, endothelial dysfunction due to reduced synthesis and/or bioavailability of NO is thought to be an early step in the course of atherosclerotic cardiovascular disease (CVD). NO is synthesized from L-arginine via the action of NO synthase (NOS), which is known to be blocked by endogenous L-arginine analogues such as asymmetric dimethylarginine (ADMA), a naturally occurring amino acid found in plasma and various types of tissues. Recently, it has been demonstrated that plasma levels of ADMA are elevated in patients with diabetes. These findings suggest that the elevated ADMA in diabetes could contribute to acceleration atherosclerosis in this population. Further, since ADMA is mainly metabolized by dimethylarginine dimethylaminohydrolase (DDAH), it is conceivable that the inhibition of ADMA via up-regulation of DDAH may be a novel therapeutic target for the prevention of CVD in patients with diabetes. In this paper, we review the pathophysiological role of ADMA and DDAH system for accelerated atherosclerosis in diabetes and the therapeutic utility of ADMA suppression in CVD in diabetes.

Keywords: Diabetic vascular complications; ADMA; oxidative stress; nitric oxide

Document Type: Research article

DOI: http://dx.doi.org/10.2174/138161208786071326

Affiliations: 1: Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume 830-0011, Japan.

Publication date: 2008-09-01

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Current Pharmaceutical Design publishes timely in-depth reviews covering all aspects of current research in rational drug design. Each issue is devoted to a single major therapeutic area. A Guest Editor who is an acknowledged authority in a therapeutic field has solicits for each issue comprehensive and timely reviews from leading researchers in the pharmaceutical industry and academia.

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Role of Asymmetric Dimethylarginine (ADMA) in Diabetic Vascular Complications

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