Role of asymmetric dimethylarginine (ADMA) in diabetic vascular complications.

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.

• Authors: Sho-ichi Yamagishi, Seiji Ueda, Kazuo Nakamura, Takanori Matsui, Seiya Okuda
• Journal: Current pharmaceutical design (Curr Pharm Des) Vol. 14 Issue 25 Pg. 2613-8 ( 2008) ISSN: 1873-4286 [Electronic] United Arab Emirates
• PMID: 18991678 (Publication Type: Journal Article, Review)

Chemical References

• N,N-dimethylarginine
• Arginine
• Nitric Oxide Synthase
• Amidohydrolases
• dimethylargininase

Topics

• Amidohydrolases (metabolism, physiology)
• Animals
• Arginine (analogs & derivatives, antagonists & inhibitors, metabolism, physiology)
• Diabetic Angiopathies (drug therapy, enzymology, metabolism, physiopathology)
• Humans
• Nitric Oxide Synthase (antagonists & inhibitors, metabolism)
• Risk Factors