Title:Asymmetric Dimethylarginine: a Key Player in the Pathophysiology of Endothelial Dysfunction, Vascular Inflammation and Atherosclerosis in Rheumatoid Arthritis?
Volume: 27
Issue: 18
Author(s): Arduino A. Mangoni*, Sara Tommasi, Salvatore Sotgia, Angelo Zinellu, Panagiotis Paliogiannis, Matteo Piga, Alberto Cauli, Gianfranco Pintus, Ciriaco Carru and Gian L. Erre
Affiliation:
- Discipline of Clinical Pharmacology, College of Medicine and Public Health, Flinders University and Flinders Medical Centre, Adelaide,Australia
Keywords:
Asymmetric dimethylarginine, rheumatoid arthritis, endothelial function, arterial stiffness, cardiovascular risk, atherosclerosis, inflammation.
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 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.
