The emerging role of symmetric dimethylarginine in vascular disease.
Asymmetric dimethylarginine (ADMA), an endogenous methylated form of the amino acid L-arginine, inhibits the activity of the enzyme endothelial nitric oxide synthase (eNOS), with consequent reduced synthesis of nitric oxide (NO). An increased synthesis and/or a reduced catabolism of ADMA might contribute to the onset and progression of atherosclerosis and thrombosis. The detrimental effects of ADMA on endothelial function, cardiovascular homeostasis, and cardiovascular outcomes have been extensively investigated. However, little attention has been paid to another methylated form of L-arginine, symmetric dimethylarginine (SDMA), as a potential modulator of vascular homeostasis and vascular disease. The first part of this chapter discusses the synthesis, transport, and metabolism of ADMA and SDMA and summarizes the evidence linking ADMA with vascular disease and adverse cardiovascular outcomes. The second part describes the results of recent studies highlighting the important role of SDMA in modulating vascular homeostasis and vascular damage. Suggestions for future research directions on SDMA are also discussed.
Department of Clinical Pharmacology, School of Medicine, Flinders University, Adelaide 5001, Australia. arduino.mangoni@flinders.edu.au
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D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000097:blood / Q000175:diagnosis / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D009569:Nitric Oxide / Q000097:blood*; D052250:Nitric Oxide Synthase Type III / Q000097:blood*; D051437:Renal Insufficiency / Q000097:blood / Q000175:diagnosis / Q000378:metabolism*
D009569:Nitric Oxide; C024917:symmetric dimethylarginine; C018524:N,N-dimethylarginine; D001120:Arginine; D052250:Nitric Oxide Synthase Type III