Matrix Metalloproteinase-9 Is Essential for Ischemia-Induced Neovascularization by Modulating Bone Marrow–Derived Endothelial Progenitor Cells

摘要: Objective— Both matrix metalloproteinases (MMPs) and endothelial progenitor cells (EPCs) have been implicated in the process of neovascularization. Here we show that impaired neovascularization mice lacking MMP-9 is related to a defect EPC functions vasculogenesis. Methods Results— Hindlimb ischemia surgery was conducted MMP-9−/− wild-type (MMP-9+/+) mice. Blood flow recovery markedly when compared with as determined by laser Doppler imaging. Flow cytometry demonstrated number EPC-like (Sca-1+/Flk-1+) peripheral blood increased after hindlimb exogenous vascular growth factor stimulation, but not Plasma levels bone marrow concentrations soluble Kit-ligand (sKitL) were significantly elevated response tissue ischemia, C-kit positive attenuated adhesion migration than those isolated from In vitro studies, incubation selective inhibitor suppressed colony formation, migration, tube formation capacities EPC. Transplantation restored collateral mice. Conclusions— These findings suggest deficiency impairs ischemia-induced neovascularization, these effects may occur through reduction releasing stem cell-active cytokine, mobilization, vasculogenesis functions.