Asymmetric Dimethyl Arginine as a Biomarker of Atherosclerosis in Rheumatoid Arthritis

Abstract

Cardiovascular disease is the main cause of morbidity and mortality in rheumatoid arthritis (RA). Despite the advent on new drugs targeting the articular manifestations, the burden of cardiovascular disease is still an unmet need in the management of RA. The pathophysiology of accelerated atherosclerosis associated to RA is not yet fully understood, and reliable and specific markers of early cardiovascular involvement are still lacking. Asymmetric dimethylarginine is gaining attention for its implication in the pathogenesis of endothelial dysfunction and as biomarkers of subclinical atherosclerosis. Moreover, the metabolic pathway of methylarginines offers possible targets for therapeutic interventions to decrease the cardiovascular risk. The purpose of this review is to describe the main causes of increased methylarginine levels in RA, their implication in accelerated atherosclerosis, the possible role as biomarkers of cardiovascular risk, and finally the available data on current pharmacological treatment.

Esophageal Squamous Cell Carcinoma Is Accompanied by Local and Systemic Changes in L-arginine/NO Pathway

“…Metabolomics is gaining interest as a potential tool in biomarker discovery [ 64 ], especially in that it enables the concomitant quantification of a predetermined panel of metabolites. The utility of individual intermediates of the L-arginine/NO pathway as biomarkers for various conditions has repeatedly been demonstrated [ 56 , 65 , 66 , 67 ]. In cancer, the simultaneous quantification of SDMA, citrulline, and DMA proved excellent in detecting CRC, and the changes in the early postoperative period in arginine, ADMA, and SDMA were an accurate marker of surgical complications [ 7 ].…”

The Biological Axis of Protein Arginine Methylation and Asymmetric Dimethylarginine

“…The scenario is further acerbated by the significantly reduced plasma arginine concentrations in patients with renal failure in comparison to healthy patients [95]. Of pathophysiological significance, elevated circulating plasma concentrations of ADMA provide a marker of risk for a wide range of endothelial dysfunction and renal and cardiovascular disorders, such as renal failure, chronic obstructive pulmonary disease (COPD) such as pulmonary arterial hypertension [97], pulmonary fibrosis, rheumatoid arthritis (RA) [98], increased cardiovascular morbidity and mortality, diabetes, heart failure, and elevated systemic blood pressure [54,99,100]. High plasma ADMA was correlated with high all-cause mortality and late mortality in renal transplant recipients.…”

Cerebrospinal fluid metabolites in tryptophan‐kynurenine and nitric oxide pathways: biomarkers for acute neuroinflammation

“…In recent years, there has been increasing attraction towards asymmetric dimethylarginine as a potential inflammatory marker in cardiovascular diseases 37 and rheumatoid arthritis. 38 Asymmetric dimethylarginine is a competitive inhibitor of nitric oxide synthase and its balance with arginine acts as an important indicator in the bioavailability of nitric oxide. 39 Neopterin is a well-established clinical inflammatory marker and the increase of the metabolite in our encephalitis cohort is strongly supported by previous cohort studies.…”

“…The higher asymmetric dimethylarginine/arginine ratio exhibited in patients with encephalitis possesses potential as an inflammatory biomarker. In recent years, there has been increasing attraction towards asymmetric dimethylarginine as a potential inflammatory marker in cardiovascular diseases 37 and rheumatoid arthritis 38 . Asymmetric dimethylarginine is a competitive inhibitor of nitric oxide synthase and its balance with arginine acts as an important indicator in the bioavailability of nitric oxide 39 …”