TY - JOUR
T1 - Asymmetric dimethylarginine
T2 - A key player in the pathophysiology of endothelial dysfunction, vascular inflammation and atherosclerosis in rheumatoid arthritis?
AU - Mangoni, Arduino A.
AU - Tommasi, Sara
AU - Sotgia, Salvatore
AU - Zinellu, Angelo
AU - Paliogiannis, Panagiotis
AU - Piga, Matteo
AU - Cauli, Alberto
AU - Pintus, Gianfranco
AU - Carru, Ciriaco
AU - Erre, Gian L.
PY - 2021
Y1 - 2021
N2 - 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 ex-act 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.
AB - 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 ex-act 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.
KW - Arterial stiffness
KW - Asymmetric dimethylarginine
KW - Atherosclerosis
KW - Cardiovascular risk
KW - Endothelial function
KW - Inflammation
KW - Rheumatoid arthritis
UR - http://www.scopus.com/inward/record.url?scp=85108636647&partnerID=8YFLogxK
U2 - 10.2174/1381612827666210106144247
DO - 10.2174/1381612827666210106144247
M3 - Review article
C2 - 33413061
AN - SCOPUS:85108636647
VL - 27
SP - 2131
EP - 2140
JO - CURRENT PHARMACEUTICAL DESIGN
JF - CURRENT PHARMACEUTICAL DESIGN
SN - 1381-6128
IS - 18
ER -