Oxidative Stress Biomarkers and Peripheral Endothelial Dysfunction in Rheumatoid Arthritis: A Monocentric Cross-Sectional Case-Control Study.

Stefania Bassu,Alberto Floris,Giuseppina Farina,Gian Luca Erre,Giuseppe Passiu,Arduino Aleksander Mangoni,Angelo Zinellu,Salvatore Sotgia,Ciriaco Carru

doi:10.3390/molecules25173855

Abstract

Previous studies have suggested that oxidative stress may heighten atherosclerotic burden in rheumatoid arthritis (RA), but direct evidence is lacking. Objective: To evaluate the relationship between established plasma oxidative stress biomarkers and peripheral endothelial dysfunction (ED), a marker of early atherosclerosis, in RA. Methods: Paroxonase-1 (PON-1), protein-SH (PSH), and malondialdehyde (MDA) were measured in 164 RA patient s and 100 age- and sex-matched healthy controls without previous cardiovascular events. Peripheral ED, evaluated by flow-mediated pulse amplitude tonometry, was defined by log-transformed reactive hyperemia index (Ln-RHI) values < 0.51. Results: PON-1 activity and PSH concentrations were significantly reduced in RA patients compared to controls. In regression analysis, increased plasma MDA levels were significantly associated with reduced Ln-RHI [B coefficient (95% CI) = −0.003 (−0.005 to −0.0008), p = 0.008] and the presence of peripheral ED (OR (95% CI) = 1.75 (1.06–2.88), p = 0.028). Contrary to our expectations, increased PON-1 activity was significantly associated, albeit weakly, with the presence of ED (OR (95% CI) = 1.00 (1.00–1.01), p = 0.017). Conclusions: In this first evidence of a link between oxidative stress and markers of atherosclerosis, MDA and PON-1 showed opposite associations with peripheral vasodilatory capacity and the presence of ED in RA. Further studies are needed to determine whether this association predicts atherosclerotic events in the RA population.

Highlights

rheumatoid arthritis (RA) is characterized by systemic complications, including atherosclerotic cardiovascular disease, that are linked to the chronic systemic inflammatory state and the dysregulated immune response [2,3]
The age, the gender distribution, and the prevalence of cardiovascular risk factors across groups were similar (Table 1), barring the mean concentration of triglycerides that was significantly higher in RA patients than in controls (Table 1)
RA patients included in the study had long-standing disease with moderate activity (Table 2)

Summary

Introduction

Rheumatoid arthritis (RA), is an autoimmune disease characterized by chronic systemic and articular inflammation, bone erosions and increased risk of all-cause and cardiovascular mortality [1].Molecules 2020, 25, 3855; doi:10.3390/molecules25173855 www.mdpi.com/journal/moleculesBeside musculoskeletal features, RA is characterized by systemic complications, including atherosclerotic cardiovascular disease, that are linked to the chronic systemic inflammatory state and the dysregulated immune response [2,3].There is good evidence that RA patients develop early endothelial dysfunction (ED), accelerated arterial wall stiffening and increased plaque burden, features of atherosclerotic disease [4,5], predisposing them to fatal cardiovascular events and sudden death [3,6]. ED and increased atherosclerotic cardiovascular disease in RA are not fully accounted for by traditional cardiovascular risk factors, suggesting that other mechanisms are likely to be involved [7,8]. Among those mechanisms, oxidative stress has been linked to functional and structural cardiovascular alterations in animal models of chronic arthritis and in patients with RA, suggesting a complex interplay between oxidative stress, autoimmune response and inflammation in the development of atherosclerotic cardiovascular disease in RA [9]. Exaggerated reactive oxygen species formation and increased levels of markers of protein and lipid oxidation have been reported in several systemic autoimmune diseases, including RA [10,11,12,13,14,15,16]

Objectives

Results

Discussion

Conclusion