It's all in the blood: circulating endothelial progenitor cells link synovial vascularity with cardiovascular mortality in rheumatoid arthritis?

The notion that angiogenesis – the formation of new blood vessels from pre-existing vasculature – is important in the perpetuation of RA synovitis is no longer novel. There is ample evidence supporting this idea, ranging from expression of proangiogenic factors such as vascular endothelial growth factor (VEGF) to studies in which inhibition of angiogenesis reduced the disease severity in animal models of arthritis [1]. However, while the rheumatologic and scientific community is in all probability now quite familiar with angiogenesis and its role in RA pathogenesis, the contribution made by EPC to blood vessel formation is less well understood. The distinct processes that result in the formation of the vasculature are vasculogenesis, which is the coalescence of endothelial cells, angiogenesis, and arteriogenesis, when the lumen of vessels increases to form collateral arteries. In the embryo, development of the vascular system occurs via a combination of vasculogenesis and angiogenesis. Formation of the primordial vascular network results from the commitment by precursor cells (haemangioblasts) to form endothelial cells, rather than haematopoietic stem cells. Following in situ differentiation of these EPC to form clusters of endothelial cells (or blood islands), these cells then multiply and interconnect to give rise to the yolk sac capillary network. Mature vessels then form by budding and re-modelling of pre-existing vessels. VEGF and its receptors are intimately involved in the regulation of both embryonic vasculogenesis and angiogenesis.Vasculogenesis has now been shown to be recapitulated in adults postnatally. EPC were first isolated from human peripheral blood by selection for cells expressing the haematopoietic maker CD34 [2]. These cells were found to differentiate into endothelial cells and to express both haematopoietic markers such as CD133 and endothelial cell markers, including CD31 and VEGF receptor type 2. Crucially, these cells also incorporated into