Abstract
Atherosclerosis and its clinical complications constitute the major healthcare problems of the world population. Due to the central role of endothelium throughout the atherosclerotic disease process, endothelial dysfunction is regarded as a common mechanism for various cardiovascular (CV) disorders. It is well established that patients with rheumatic autoimmune diseases are characterized by significantly increased prevalence of cardiovascular morbidity and mortality compared with the general population. The current European guidelines on cardiovascular disease (CVD) prevention in clinical practice recommend to use a 1,5-factor multiplier for CV risk in rheumatoid arthritis as well as in other autoimmune inflammatory diseases. However, mechanisms of accelerated atherosclerosis in these diseases, especially in the absence of traditional risk factors, still remain unclear. Oxidative stress plays the major role in the endothelial dysfunction and recently is strongly attributed to endothelial NO synthase dysfunction (eNOS uncoupling). Converted to a superoxide-producing enzyme, uncoupled eNOS not only leads to reduction of the nitric oxide (NO) generation but also potentiates the preexisting oxidative stress, which contributes significantly to atherogenesis. However, to date, there are no systemic analyses on the role of eNOS uncoupling in the excess CV mortality linked with autoimmune rheumatic diseases. The current review paper addresses this issue.
Highlights
Atherosclerosis and its clinical complications constitute the major healthcare problems of the world population [1,2,3]
Rheumatoid Arthritis (RA) disease-related inflammation may contribute to elevated asymmetric dimethylarginine (ADMA) levels and increased cardiovascular disease (CVD) risk in RA, the association between ADMA and disease activity has been an issue of debate, as previous studies are heterogenous in results
Given the evident role of TNF in atherosclerosis and RA pathogenesis and its inhibitory effect on dimethylarginine dimethylaminohydrolase (DDAH) leading to ADMA accumulation, a beneficial effect of TNF inhibition has been postulated; results of conducted studies did not demonstrate a consistent decrease in ADMA levels with subsequent improvement in vascular morphology and function suggesting that the ADMA level does not seem to be a straightforward indicator of endothelial dysfunction and subclinical atherosclerosis in rheumatic diseases
Summary
Atherosclerosis and its clinical complications constitute the major healthcare problems of the world population [1,2,3]. Endothelial dysfunction (ED), the early feature of atherosclerosis, precedes the development of morphologic changes and is the earliest detectable impairment of vascular function [4, 5] It is a consequence of chronic exposure to cardiovascular (CV) risk factors, and its progression is related to the intensity and duration of these factors [6, 7]. Decreased NO bioavailability may result from its limited production and/or increased NO degradation by reactive oxygen species (ROS) (Figure).ReducedNOgenerationcanbeduetodecreasedendothelial NO synthase (eNOS) expression and/or activity, eNOS uncoupling, impaired NO-mediated signaling events, and oxidative stress. Among these mechanisms, the eNOS uncoupling has recently attracted the gaining attentions.
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