A growing body of evidence outlines the key roles of circulating endothelial progenitor cells (EPCs) in vascular repair and angiogenesis. Several mechanisms have been proposed to explain the beneficial effects of EPCs. It was reported that EPCs participate in the reendothelialization process after arterial injury.1 However, under pathological conditions such as diabetes mellitus, hypertension, dyslipidemia, and aging, the functional capacities of EPCs appear to be impaired.2 Thus, it is of clinical importance to elucidate the molecular signaling that ameliorates EPC function. In this issue of Arteriosclerosis, Thrombosis, and Vascular Biology , Kawabe et al3 report that prostaglandin I2(PGI2) improves EPC function via a PGI2 receptor, which is termed IP receptor. Like many other lipid mediators of the eicosanoid family, PGI2 is produced by the PGI2 synthase coupled to cyclooxygenase (COX) system. COX involves either COX-1 or COX-2, depending on the cell type and the biological context.4 Although numerous articles have shown the antiplatelet and vasodilating properties of PGI2,5 the beneficial effects of this lipid molecule on EPCs and reendothelialization have not yet been investigated. See accompanying article on page 464 To gain insights into the role of the PGI2-IP axis in the regulation of EPC function, the authors performed bone …