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

Oxid Med Cell Longev. 2020 Apr 13:2020:1417981. doi: 10.1155/2020/1417981. eCollection 2020.

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.

Publication types

  • Review

MeSH terms

  • Animals
  • Autoimmune Diseases / enzymology
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / metabolism*
  • Humans
  • Metabolic Networks and Pathways
  • Nitric Oxide / metabolism*
  • Nitric Oxide Synthase Type III / metabolism*
  • Rheumatic Diseases / enzymology
  • Rheumatic Diseases / immunology
  • Rheumatic Diseases / metabolism*
  • Signal Transduction

Substances

  • Nitric Oxide
  • Nitric Oxide Synthase Type III