Vascular trauma induces rapid but transient mobilization of VEGFR2(+)AC133(+) endothelial precursor cells

Bone marrow (BM)-derived circulating endothelial precursor cells (CEPs) are thought to play a role in postnatal angiogenesis. Emerging evidence sugges ts that angiogenic stress of vascular trauma may induce mobilization of CEP s to the peripheral circulation. In this regard, we studied the kinetics of CEP mobilization in two groups of patients who experienced acute vascular insult secondary to burns or coronary artery bypass grafting (CABG). In bot h burn and CABG patients, there was a consistent, rapid increase in the num ber of CEPs, determined by their surface expression pattern of vascular end othelial growth factor receptor 2 (VEGFR2), vascular endothelial cadherin ( VE-cadherin), and AC133, Within the first 6 to 12 hours after injury, the p ercentage of CEPs in the peripheral blood of burn or CABG patients increase d almost 50-fold, returning to basal levels within 48 to 72 hours. Mobilize d cells also formed late-outgrowth endothelial colonies (CFU-ECs) in cultur e, indicating that a small, but significant, number of circulating endothel ial cells were PM-derived CEPs. In parallel to the mobilization of CEPs, th ere was also a rapid elevation of VEGF plasma levels. Maximum VEGF levels w ere detected within 6 to 12 hours of vascular trauma and decreased to basel ine levels after 48 to 72 hours. Acute elevation of VEGF in the mice plasma resulted in a similar kinetics of mobilization of VEGFR2(+) cells. On the basis of these results, we propose that vascular trauma may induce release of chemokines, such as VEGF, that promotes rapid mobilization of CEPs to th e peripheral circulation. Strategies to improve the mobilization and incorp oration of CEPs may contribute to the acceleration of vascularization of th e injured vascular tissue.