Asymmetrical dimethylarginine, oxidative stress, and atherosclerosis.

Asymmetrical Dimethylarginine, Oxidative Stress, and Atherosclerosis To the Editor: Antoniades et al1 reported on the role of asymmetrical dimethylarginine (ADMA) in inflammation-induced endothelial dysfunction in healthy subjects and in patients with coronary artery disease or rheumatoid arthritis. In patients with chronic inflammatory rheumatic diseases, serum nitrite concentrations were lower compared with healthy subjects but higher in the patients’ synovial fluid, suggesting impaired endothelial NO synthase activity but increased inducible NO synthase activity in the inflamed joint.2 In coronary artery disease patients without rheumatoid arthritis,3 as well as in rheumatoid arthritis patients without coronary artery disease, both ADMA synthesis and dimethylarginine dimethylaminohydrolase activity are severalfold elevated compared with healthy controls (Figure A). Dimethylamine (r 0.66; P 0.07) and ADMA (r 0.79; P 0.02) correlated with 3-nitrotyrosine (Figure B), a potential biomarker of myeloperoxidase activity.2 These findings support the conclusion by Antoniades et al1 that ADMA may be both a link between inflammation and endothelial dysfunction and a potential therapeutic strategy for the treatment of inflammation-related endothelial dysfunction. ADMA is a weak inhibitor of endothelial NO synthase (IC50, 12 mol/L). Also, ADMA plasma concentration only changes a little (by approximately 15%) on disease or pharmacological treatment. Other more potent mechanisms, such as ADMAinduced suppression/depletion of endothelial progenitor cells,4,5 are likely to be involved in coronary artery disease and rheumatoid arthritis. Systemic inflammation and elevated ADMA synthesis are common to many diseases, but ADMA elimination may vary considerably. Measurements of ADMA and dimethylamine in urine rather than ADMA in plasma may be more useful parameters to optimize treatment of inflammation-related endothelial dysfunction. Disclosures None.