Relationship between asymmetric dimethylarginine and endothelial dysfunction in patients with rheumatoid arthritis

Abstract

Objective: In rheumatoid arthritis (RA), endothelial dysfunction caused by the inflammatory process increases the risk of cardiovascular disease. Asymmetric Dimethylarginine (ADMA) leads to vascular dysfunction, whereas atherosclerosis and increased ADMA is associated with cardiovascular disease risk factors. Flow-mediated Dilation (FMD) is a radiological method to demonstrate endothelial dysfunction. In the present study, we assessed the availability of ADMA as a marker for endothelial dysfunction in RA patients. ADMA can be used as a simple and cheaper method for the determination of endothelial dysfunction. Material and Methods:Forty patients (1 male, 39 female) diagnosed with RA according to the classification criteria and 29 healthy volunteers (2 males, 27 females) were included in this study. ADMA was studied by enzyme-linked immunosorbent assay (ELISA). Chi-square, Fisher's exact test, Mann-Whitney U test, and Spearman's correlation tests were used for analytical analysis, and p<0.05 was considered as the level of statistical significance.Results: In our study, ADMA levels were significantly higher in RA patients. The ADMA level was inversely correlated with FMD.

Psoriasis as the single risk factor for “Locked-in syndrome” after ischemic stroke in a young patient: case report and literature review

“…Endothelial dysfunction has been shown in autoimmune disease patients like rheumatoid arthritis. Reduced number and impaired function of endothelial progenitor cells, impaired responsiveness to nitric oxide (NO), elevated level of monocyte chemotactic protein-1 (MCP-1)induced protein and elevated level of asymmetric dimethylarginine are among the most important contributors to endothelial dysfunction in autoimmune disease [10][11][12][13]. Early arterial stiffness and calcification are also involved in the development of CAD and stroke in autoimmune diseases patient [14,15].…”

Role of the eNOS Uncoupling and the Nitric Oxide Metabolic Pathway in the Pathogenesis of Autoimmune Rheumatic Diseases

“…Negative regulation of NO synthesis can also be mediated through overproduction of methylated arginine analogues such as ADMA. Recently, many clinical studies have demonstrated that plasma levels of ADMA were elevated in RA patients regardless of the presence of cardiovascular disease [55][56][57][58][59][60][61][62][63][64][65][66][67]. Furthermore, ADMA has been reported to be related to indices of endothelial dysfunction or subclinical atherosclerosis in some [56,65,68], but not all, conducted studies [58,60,61,67,68].…”

“…Recently, many clinical studies have demonstrated that plasma levels of ADMA were elevated in RA patients regardless of the presence of cardiovascular disease [55][56][57][58][59][60][61][62][63][64][65][66][67]. Furthermore, ADMA has been reported to be related to indices of endothelial dysfunction or subclinical atherosclerosis in some [56,65,68], but not all, conducted studies [58,60,61,67,68]. In patients with high disease activity and no overt atherosclerotic disease or classic risk factors, high plasma ADMA levels significantly correlated with IMT [67], coronary flow reserve (CFR) [56], and pulse wave velocity (PWV) [58], whereas in those with evident atherosclerosis and CV risk factors, negative correlation between ADMA and FMD [65] and carotid IMT (cIMT) [62,68] was found.…”

“…Furthermore, ADMA has been reported to be related to indices of endothelial dysfunction or subclinical atherosclerosis in some [56,65,68], but not all, conducted studies [58,60,61,67,68]. In patients with high disease activity and no overt atherosclerotic disease or classic risk factors, high plasma ADMA levels significantly correlated with IMT [67], coronary flow reserve (CFR) [56], and pulse wave velocity (PWV) [58], whereas in those with evident atherosclerosis and CV risk factors, negative correlation between ADMA and FMD [65] and carotid IMT (cIMT) [62,68] was found. In the latter subgroup of patients also, a positive relation was observed between the ADMA : SDMA ratio (suggested as the index of dimethylarginine dimethylaminohydrolase activity) and microvascular endothelial function [68] and arterial stiffness [62].…”

“…In the latter subgroup of patients also, a positive relation was observed between the ADMA : SDMA ratio (suggested as the index of dimethylarginine dimethylaminohydrolase activity) and microvascular endothelial function [68] and arterial stiffness [62]. However, these relationships were not observed in RA patients with low and moderate disease activities-although structural and functional changes in vessels and heart were detected by means of multiple noninvasive, validated methods including cIMT, FMD, CFR, PWV, laser Doppler, and subendocardial viability ratio (SEVR), no associations between dimethylarginines and assessments of vascular morphology and function were found [56,61,65]. As an explanation of these findings, it has been suggested that inflammatory mechanisms responsible for synovial lesions might also occur in the vascular wall and promote the development of advanced atherosclerosis.…”