Endothelial progenitor cells as cardiovascular surrogate markers in seropositive rheumatoid arthritis

Abstract

Background Bone marrow-derived endothelial progenitor cells (EPCs) confer protection against atherosclerotic vascular damage, thereby reducing the cardiovascular (CV) risk. Hence, the depletion of EPCs in rheumatoid arthritis (RA) is associated with enhanced CV risk. Patients with seropositive RA have increased risk of CV morbidity and mortality. The aim of this study was to investigate the endothelial progenitor cell population in seropositive and seronegative RA patients and its potential relationships with disease variables and proinflammatory cytokines. Methods Forty adult RA patients were classified into seropositive (n = 20) and seronegative (n = 20) groups based on the presence of rheumatoid factor (RF). EPCs (CD34+/CD133+) quantified by flow cytometry and proinflammatory cytokines (TNF- α, IL-6 and IL-1) were measured using standard ELISA kits, and disease activity by DAS28, CRP, and ESR. Results EPCs were significantly reduced in total RA and seropositive patients compared to seronegative subjects (P <0.05).  Levels of proinflammatory cytokines (TNF-α, IL-6, and IL-1) were significantly (P = 0.01) higher in seropositive patients as compared to seronegative but in total RA patients level of IL-6 and IL-1 were significantly (P <0.05) higher as compared to seronegative patients. Significant negative correlation was observed between percentage of EPCs and IL-1, TNF-α, and disease activity in seropositive patients, between RF and TNF-α in seropositive patients, and between EPCs and DAS 28 in total RA patients. Conclusion EPC depletion is inversely correlated with disease activity, RF, and proinflammatory cytokines in seropositive patients, suggesting the pivotal role of inflammation in depletion of EPCs. EPC may serve as a probable therapeutic target for preventing cardiovascular disease in seropositive RA.