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.

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

Piga M.;Cauli A.;
2021

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 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.
Arterial stiffness
Asymmetric dimethylarginine
Atherosclerosis
Cardiovascular risk
Endothelial function
Inflammation
Rheumatoid arthritis
Arginine
Endothelial Cells
Endothelium, Vascular
Humans
Inflammation
Nitric Oxide
Arthritis, Rheumatoid
Atherosclerosis
File in questo prodotto:
File Dimensione Formato  
Text_030720.docx

non disponibili

Tipologia: versione post-print
Dimensione 5.02 MB
Formato Microsoft Word XML
5.02 MB Microsoft Word XML   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11584/335249
Citazioni
  • ???jsp.display-item.citation.pmc??? 2
  • Scopus 4
  • ???jsp.display-item.citation.isi??? 2
social impact