Nitric Oxide: Link between Inflammation and Endothelial Dysfunction in Rheumatoid Arthritis

Abstract

Nitric oxide (NO) plays an important role in inflammatory joint disease and endothelial function. Endothelial dysfunction has been attributed to a reduction in NO bioactivity in rheumatoid arthritis (RA). However, the relationship of NO with inflammation and endothelial dysfunction in RA has not yet been investigated. To investigate the relationship of nitrite with inflammation and endothelial dysfunction in RA. Total 28 patients satisfying 2010 Rheumatoid Arthritis Classification Criteria were recruited for the study. Serum nitrite estimation was performed by Griess reaction. Flow-mediated dilation (FMD) assessed using AngioDefender. Inflammatory disease activity measures included disease activity score of 28 joints (DAS28), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). Proinflammatory cytokines (TNF-α, IL-6, and IL-1) measured using standard ELISA kits. Twenty-five healthy controls matched for age and sex were included for comparison. The serum nitrite level in patients with RA was markedly elevated as compared with controls ( < 0.05). FMD was significantly impaired in RA patients than controls ( < 0.05). DAS28 was significantly higher in RA patients ( < 0.05). Levels of ESR, CRP, TNF-α, IL-1, and IL-6 were significantly higher in RA patients than controls ( < 0.05). Significant positive correlation was observed between nitrite and CRP ( = 0.46, < 0.05), TNF-α ( = 0.53, < 0.05), and inverse correlation with FMD ( =0.62, < 0.05). Inflammatory disease activity and endothelial dysfunction in RA are associated with increased concentration of proinflammatory cytokines and NO. Inflammatory triggered release of cytokines induced NO production that mediates endothelial dysfunction. These findings suggest a role for NO in inflammation-induced endothelial dysfunction in RA.

Serum levels of 14‑3‑3η are associated with increased disease risk, activity and duration of rheumatoid arthritis in Chinese patients

“…Another study by the same group further demonstrated that stimulation of THP-1 cells by 14-3-3η induced the release of inflammatory transcripts, including IL-1β, IL-6, MMP-1, MMP-3 and receptor activator of NF-κB ligand (RANKL) ( 24 ). Numerous studies have indicated that IL-1β and IL-6 participate in the inflammatory processes of RA ( 26-28 ), while MMP-1, MMP-3 and RANKL have been demonstrated to exert important roles in joint damage ( 29-32 ). Therefore, 14-3-3η may increase inflammatory activity and joint damage in patients with RA through regulating IL-1β, IL-6, MMP-1, MMP-3 and RANKL, which may explain its predictive effect for the risk of RA revealed in the present study.…”

The Effects of Rheumatoid Arthritis on In-Hospital Lengths of Stay, Complications, and Costs following Primary Total Hip Arthroplasty: A Matched-Control Study

“…[36][37][38] Other studies have shown that RA leads to endothelial dysfunction and injury at the cellular level. [39][40][41][42] These hematological derangements in RA patients possibly contribute to Virchow's triad and may explain the increased frequency of thromboembolic complications in RA patients observed in this study.…”

Traditional and Non-Traditional Risk Factors Involved with Endothelial Dysfunction and Arterial Stiffness in Autoimmune Rheumatic Diseases

“…The most frequently described TRFs for CVD in RA are smoking, sedentary behavior and dyslipidemia [1] [16], whereas mainly non-TRFs are factors in this disease's chronic and systemic inflammatory process [17] [18], as shown in Table 1.…”

“…It has also been shown that IL-1/TNF can cause alterations in serum concentrations of homocysteine, leading to the production of asymmetric dimethylarginine, which negatively affects the regulating expression of nitric oxide synthase (NOS) [17].…”