In addition to the well-documented roles of interaction of EPCs with platelets at the sites of vascular injury mainly within the thrombi and along the vessel wall, our findings highlight a new biological role for platelets in regulating EPC function via SDF-1α, VEGF, CD40L, PDGF, IL-1β,-6,-8 chemokines, miR-223, and IGF-1R in atherosclerosis. The gene discussed is CD40LG; the disease is atherosclerosis.