Circulation. 2004;109:1813-1818
doi: 10.1161/01.CIR.0000126823.07732.D5
doi: 10.1161/01.CIR.0000126823.07732.D5
(Circulation. 2004;109:1813-1818.)
© 2004 American Heart Association, Inc.
Special Review |
Asymmetrical Dimethylarginine
The Über Marker?
From the Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, Calif.
Correspondence to John P. Cooke, MD, PhD, Division of Cardiovascular Medicine, Stanford University School of Medicine, 300 Pasteur Dr, Stanford, CA 94305. E-mail john.cooke@stanford.edu
Key Words: arginine • nitric oxide synthase • endothelium • risk factors • amidohydrolases
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
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Introduction |
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The traditional risk factors of hypercholesterolemia, hypertension, diabetes mellitus, and tobacco exposure identify a subset of patients at greater cardiovascular risk. A variety of clinical phenotypes, biochemical markers, and genetic polymorphisms have been proposed to explain the variance in risk not explained by the traditional factors. Notably, all of the traditional risk factors, as well as the great majority of new risk markers, are associated with endothelial vasodilator dysfunction.
Because the end points (endothelial dysfunction leading to plaque formation, progression, and rupture) are the same, it follows that diverse risk factors ultimately share common pathways(s) of pathobiology. We and others have provided evidence for a ubiquitous mechanism of endothelial pathobiology shared by all risk factors and markers examined to date. This mechanism of endothelial derangement is mediated by an endogenous inhibitor of nitric oxide synthase (NOS), a molecule known as asymmetrical dimethylarginine (ADMA). Risk factors impair endothelial vasodilator function by causing the accumulation of ADMA. Furthermore, by blocking NO generation, ADMA initiates and promotes processes involved in atherogenesis, plaque progression. and plaque rupture. This review examines the burgeoning body of literature that supports ADMA as an "Über marker," a biochemical factor mediating the adverse vascular effects of many other risk factors and markers.
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ADMA: A Major Cause of Endothelial Dysfunction |
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Endothelial NOS converts the amino acid L-arginine into L-citrulline and NO. The importance of NO in vascular homeostasis has been discussed elsewhere.1 In addition to its vasodilator activity, NO inhibits key processes involved in vascular disease, including leukocyte adhesion, platelet aggregation, and vascular smooth muscle
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