Role of kinin B2 receptor signaling in the recruitment of circulating progenitor cells with neovascularization potential

摘要: Reduced migratory function of circulating angiogenic progenitor cells (CPCs) has been associated with impaired neovascularization in patients cardiovascular disease (CVD). Previous findings underline the role kallikrein-kinin system angiogenesis. We now demonstrate involvement kinin B2 receptor (B(2)R) recruitment CPCs to sites ischemia and their proangiogenic action. In healthy subjects, B(2)R was abundantly present on CD133(+) CD34(+) as well cultured endothelial (EPCs) derived from blood mononuclear (MNCs), whereas B1 expression barely detectable. transwell migration assays, bradykinin (BK) exerts a potent chemoattractant activity EPCs via B(2)R/phosphoinositide 3-kinase/eNOS-mediated mechanism. Migration toward BK able attract an MNC subpopulation enriched vitro activity, assessed by Matrigel assay. showed low levels decreased capacity BK. When injected systemically into wild-type mice unilateral limb ischemia, bone marrow MNCs syngenic B(2)R-deficient resulted reduced homing sca-1(+) cKit(+)flk1(+) progenitors ischemic muscles, reparative neovascularization, delayed perfusion recovery compared MNCs. Similarly, blockade systemic administration icatibant prevented beneficial effect transplantation. BK-induced represents novel mechanism mediating progenitors. Reduction sensitivity might contribute after complications.