Asymmetric dimethylarginine: a key player in the pathophysiology of endothelial dysfunction, vascular inflammation and atherosclerosis in rheumatoid arthritis?

• Published in: Current pharmaceutical design
• Main Authors: Mangoni, Arduino A, Tommasi, Sara, Sotgia, Salvatore, Zinellu, Angelo, Paliogiannis, Panagiotis, Piga, Matteo, Cauli, Alberto, Pintus, Gianfranco, Carru, Ciriaco, Erre, Gian Luca
• Format: Journal Article
• Language: English
• Published: United Arab Emirates 01.01.2021
• Subjects: arterial stiffness; atherosclerosis; endothelial function; inflammation; cardiovascular risk; rheumatoid arthritis; asymmetric dimethylarginine
• ISSN: 1873-4286
• DOI: 10.2174/1381612827666210106144247

Patients with rheumatoid arthritis (RA), a chronic and disabling autoimmune condition that is characterized by articular and extra-articular manifestations and a pro-inflammatory and pro-oxidant state, suffer from premature atherosclerosis and excessive cardiovascular disease burden. A key step in the pathogenesis of atherosclerosis is the impaired synthesis of the endogenous messenger nitric oxide (NO) by endothelial cells which, in turn, alters local homeostatic mechanisms and favors vascular damage and plaque deposition. While the exact mechanisms of endothelial dysfunction in RA remain to be established, there is good evidence that RA patients have relatively high circulating concentrations of the methylated arginine asymmetric dimethylarginine (ADMA), a potent endogenous inhibitor of endothelial NO synthase (eNOS). This review discusses the biological and pathophysiological role of ADMA, the interplay between ADMA, inflammation and oxidative stress, and the available evidence on the adverse impact of ADMA on endothelial function and atherosclerosis and potential ADMA-lowering therapies in RA patients.