Vasculogenesis in rheumatoid arthritis

Endothelial progenitor cells (EPCs) are hematopoietic stem cells expressing CD34, CD133, type 2 vascular endothelial growth factor (VEGF) receptor (VEGFR-2 or Flk-1), and the CXCR4 chemokine receptor [1-4]. During vasculogenesis, EPCs are mobilized from the bone marrow and they differentiate into mature endothelial cells [3]. Under normal conditions, vasculogenesis is involved in both prenatal and postnatal tissue development, vascular repair, and atherosclerosis [2,3].In rheumatoid arthritis (RA), several groups have described defective vasculogenesis related to impaired EPC numbers and functions in RA [4-6]. Impaired vasculogenesis has been associated with increased cardiovascular morbidity and mortality in RA [7,8]. Effective antirheumatic therapy, such as corticosteroids and tumor necrosis factor-alpha (TNF-α) blockers, may stimulate the outgrowth and function of EPCs and thus may restore defective vasculogenesis in arthritis [5]. In addition, as the induction of vasculogenesis may be beneficial for patients with cardiovascular disease [8], the stimulation of EPCs and vasculogenesis may also suppress premature atherosclerosis underlying RA [7].In the previous issue of Arthritis Research & Therapy, Jodon de Villeroché and colleagues [1] assessed late-outgrowth EPCs in RA and found increased colony-formation capacity of these cells in RA. Furthermore, higher or lower EPC numbers correlated with active disease and disease in remission, respectively. These results seem to be somewhat controversial as a number of other investigators reported defective EPC function in RA and lower EPC numbers in active RA [5,6]. There has been only one report by the same group, Allanore and colleagues [9], suggesting that circulating EPC numbers may be higher in RA. Nevertheless, Jodon de Villeroché and colleagues [1] conducted an approach that was significantly different from that of others. Instead of analyzing all EPCs, they differentiated two EPC sub-populations, namely EPCs of mo