Enhanced late-outgrowth circulating endothelial progenitor cell levels in rheumatoid arthritis and correlation with disease activity

Abstract

Angiogenesis and vasculogenesis are critical in rheumatoid arthritis (RA) as they could be a key issue for chronic synovitis. Contradictory results have been published regarding circulating endothelial progenitor cells (EPCs) in RA. We herein investigated late outgrowth EPC sub-population using recent recommendations in patients with RA and healthy controls. EPCs, defined as Lin-/7AAD-/CD34+/CD133+/VEGFR-2+ cells, were quantified by flow cytometry in peripheral blood mononuclear cells (PBMCs) from 59 RA patients (mean age: 54 ± 15 years, disease duration: 16 ± 11 years) and 36 controls (mean age: 53 ± 19 years) free of cardiovascular events and of cardiovascular risk factors. Concomitantly, late outgrowth endothelial cell colonies derived from culture of PBMCs were analyzed by colony-forming units (CFUs). RA patients displayed higher circulating EPC counts than controls (median 112 [27 to 588] vs. 60 [5 to 275]) per million Lin- mononuclear cells; P = 0.0007). The number of circulating EPCs positively correlated with disease activity reflected by DAS-28 score (r = 0.43; P = 0.0028) and lower counts were found in RA patients fulfilling remission criteria (P = 0.0069). Furthermore, late outgrowth CFU number was increased in RA patients compared to controls. In RA, there was no association between the number of EPCs and serum markers of inflammation or endothelial injury or synovitis. Our data, based on a well characterized definition of late outgrowth EPCs, demonstrate enhanced levels in RA and relationship with disease activity. This supports the contribution of vasculogenesis in the inflammatory articular process that occurs in RA by mobilization of EPCs.