Roles of aberrant endothelial progenitor cells in pathogenesis of systemic sclerosis

Abstract

Systemic sclerosis (SSc) is a multisystem connective tissue disease characterized by excessive fibrosis andmicrovasculopathy, along with poor vascular formation and repair. The maintenance of the postnatal vascular systemrequires constant remodeling through vasculogenesis, which is mediated by the de novo diFFerentiation of mature endothelialcells from endothelial progenitor cells (EPCs). However, a great deal of controversy about EPCs and theirroles in postnatal vascular formation has arisen because of discrepancies in how EPCs are den̂ed. The current consensusis that EPCs are heterogeneous cell population containing an extremely small count of "true EPCs", and pro-angiogenichematopoietic cells (PHCs) that promotes vascular formation and repair through secretion of pro-angiogenicfactors, and diFFerentiation into endothelial cells and mural cells. In 2004, we reported a reduced number and impairedfunction of circulating CD34+CD133+CD309+CD45dimCD14-FF0D EPCs, which are now regarded as an immature subsetof PHCs, in patients with SSc, and proposed a theory that defective vascular repair machinery as one of importantmechanisms contributing to SSc vasculopathy. In addition, we showed that in SSc patients, circulating monocyticPHCs were increased and have enhanced angiogenic potency and differentiation potential to fibroblast-like cells. Insummary, EPCs are involved in the pathogenesis of SSc by participating in two major pathological features, microvasculopathyand excessive fibrosis. Understanding the roles of EPCs in disease process of SSc may be key to dissecting itspathogenesis and to developing novel therapeutic strategies for this intractable condition. © 2013 The Japan Society for Clinical Immunology.