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Asymmetric Dimethylarginine: a Key Player in the Pathophysiology of Endothelial Dysfunction, Vascular Inflammation and Atherosclerosis in Rheumatoid Arthritis?

Author(s):

Arduino A Mangoni*, Sara Tommasi, Salvatore Sotgia, Angelo Zinellu, Panagiotis Paliogiannis, Matteo Piga, Alberto Cauli, Gianfranco Pintus, Ciriaco Carru and Gian Luca Erre   Pages 1 - 10 ( 10 )

Abstract:


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.

Keywords:

asymmetric dimethylarginine, rheumatoid arthritis, endothelial function, arterial stiffness, cardiovascular risk, atherosclerosis, inflammation.

Affiliation:

Discipline of Clinical Pharmacology, College of Medicine and Public Health, Flinders University and Flinders Medical Centre, Adelaide, Discipline of Clinical Pharmacology, College of Medicine and Public Health, Flinders University and Flinders Medical Centre, Adelaide, Department of Biomedical Sciences, University of Sassari, Sassari, Department of Biomedical Sciences, University of Sassari, Sassari, Department of Medical, Surgical and Experimental Sciences, University of Sassari, Sassari, Rheumatology Unit, University Clinic and AOU of Cagliari, Cagliari, Rheumatology Unit, University Clinic and AOU of Cagliari, Cagliari, Department of Biomedical Sciences, University of Sassari, Sassari, Department of Biomedical Sciences, University of Sassari, Sassari, Rheumatology Unit, Department of Clinical and Experimental Medicine, University Hospital (AOUSS) and University of Sassari, Sassari



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