doi: 10.1161/01.ATV.0000040860.71626.9D
© 2003 American Heart Association, Inc.
Editorials |
Adverse Effects of Supplemental L-Arginine in Atherosclerosis
Consequences of Methylation Stress in a Complex Catabolism?
From the Whitaker Cardiovascular Institute and Evans Department of Medicine, Boston University School of Medicine, Mass.
Address correspondence to Joseph Loscalzo, MD, PhD, Whitaker Cardiovascular Institute, 715 Albany St, W507, Boston, MA, 02118-2394. E-mail jloscalz@bu.edu
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
Atherothrombosis and its risk factors are associated with endothelial dysfunction,1 one manifestation of which is inadequate production of bioactive endothelial NO. Two basic mechanisms account for the loss of endothelial NO: decreased synthesis and increased oxidative inactivation. In the atherothrombotic vessel, both mechanisms appear to be active. Vascular production of reactive oxygen species creates an environment in which NO can be oxidatively inactivated to peroxynitrite and other derivatives. The sources of one of these reactive oxygen species—superoxide anion—include NAD(P)H oxidase elaborated on the plasma membrane of leukocytes, endothelial cells, and vascular smooth muscle cells; mitochondria; and the NO synthases. Both endothelial NO synthase (eNOS) and inducible NO synthase (iNOS) isoforms are expressed in the atherothrombotic vasculature and, owing to a loss of substrate or reducing cofactors required for NO synthesis, undergo enzymatic "uncoupling" leading to both a loss of NO production and an increase in superoxide anion generation.
See page 97
The semiessential amino acid L-arginine is the principal substrate of the NO synthases, which catalyze its five-electron oxidation to L-citrulline and NO. As early as 1992, Creager and colleagues2 showed that supplemental dietary L-arginine improved endothelial vasodilator response in hypercholesterolemic subjects, and Dubois-Rande and coworkers3 showed that intravenous L-arginine improved endothelial vasodilator response in patients with atheromatous left anterior descending coronary arteries. These initial observations were followed by numerous studies supporting the benefits of acute and chronic L-arginine supplementation on endothelial NO production in animal models and human subjects.
These studies were all predicated
This article has been cited by other articles:
 |
|
 |
|
  G. Pare, D. I. Chasman, A. N. Parker, R. R.Y. Zee, A. Malarstig, U. Seedorf, R. Collins, H. Watkins, A. Hamsten, J. P. Miletich, et al. Novel Associations of CPS1, MUT, NOX4, and DPEP1 With Plasma Homocysteine in a Healthy Population: A Genome-Wide Evaluation of 13 974 Participants in the Women's Genome Health Study Circ Cardiovasc Genet, April 1, 2009; 2(2): 142 - 150. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Loscalzo Homocysteine Trials -- Clear Outcomes for Complex Reasons N. Engl. J. Med., April 13, 2006; 354(15): 1629 - 1632. [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Yang and X.-F. Ming Recent advances in understanding endothelial dysfunction in atherosclerosis. Clin. Med. Res., March 1, 2006; 4(1): 53 - 65. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. J. Rabelink and T. F. Luscher Endothelial Nitric Oxide Synthase: Host Defense Enzyme of the Endothelium? Arterioscler Thromb Vasc Biol, February 1, 2006; 26(2): 267 - 271. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. P. Schulman, L. C. Becker, D. A. Kass, H. C. Champion, M. L. Terrin, S. Forman, K. V. Ernst, M. D. Kelemen, S. N. Townsend, A. Capriotti, et al. L-Arginine Therapy in Acute Myocardial Infarction: The Vascular Interaction With Age in Myocardial Infarction (VINTAGE MI) Randomized Clinical Trial JAMA, January 4, 2006; 295(1): 58 - 64. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M Morris JR Arginine metabolism in vascular biology and disease Vascular Medicine, July 1, 2005; 10(1_suppl): S83 - S87. [Abstract] [PDF]
|
|
|
|
 |
|
 M. S. Goligorsky Endothelial cell dysfunction: can't live with it, how to live without it Am J Physiol Renal Physiol, May 1, 2005; 288(5): F871 - F880. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M Morris Jr Arginine metabolism in vascular biology and disease Vascular Medicine, May 1, 2005; 10(2_suppl): S83 - S87. [Abstract] [PDF]
|
|
|
|
 |
|
 C. L. Ulrey, L. Liu, L. G. Andrews, and T. O. Tollefsbol The impact of metabolism on DNA methylation Hum. Mol. Genet., April 15, 2005; 14(suppl_1): R139 - R147. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. G. West, A. Likos-Krick, P. Brown, and F. Mariotti Oral L-Arginine Improves Hemodynamic Responses to Stress and Reduces Plasma Homocysteine in Hypercholesterolemic Men J. Nutr., February 1, 2005; 135(2): 212 - 217. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. L. Gornik and M. A. Creager Arginine and Endothelial and Vascular Health J. Nutr., October 1, 2004; 134(10): 2880S - 2887S. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. L. Goodwin, L. P. Solomonson, and D. C. Eichler Argininosuccinate Synthase Expression Is Required to Maintain Nitric Oxide Production and Cell Viability in Aortic Endothelial Cells J. Biol. Chem., April 30, 2004; 279(18): 18353 - 18360. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. P. Solomonson, B. R. Flam, L. C. Pendleton, B. L. Goodwin, and D. C. Eichler The caveolar nitric oxide synthase/arginine regeneration system for NO production in endothelial cells J. Exp. Biol., June 15, 2003; 206(12): 2083 - 2087. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. P. Cooke, K. Sydow, J. Chen, and P. Huang A Peculiar Result and a Fanciful Hypothesis Regarding L-Arginine * Arterioscler Thromb Vasc Biol, June 1, 2003; 23(6): 1128 - 1128. [Full Text] [PDF]
|
|
|
|
|
|
V. R. Young Introduction to the 2nd Amino Acid Assessment Workshop J. Nutr., June 1, 2003; 133(6): 2015S - 2020. [Abstract] [Full Text] [PDF]
|
|