Abstract
OBJECTIVE-: Both matrix metalloproteinases (MMPs) and endothelial progenitor cells (EPCs) have been implicated in the process of neovascularization. Here we show that the impaired neovascularization in mice lacking MMP-9 is related to a defect in EPC functions in vasculogenesis. METHODS AND RESULTS-: Hindlimb ischemia surgery was conducted in MMP-9 mice and wild-type (MMP-9) mice. Blood flow recovery was markedly impaired in MMP-9 mice when compared with that in wild-type mice as determined by laser Doppler imaging. Flow cytometry demonstrated that the number of EPC-like cells (Sca-1/Flk-1) in peripheral blood increased in wild-type mice after hindlimb ischemia surgery and exogenous vascular endothelial growth factor stimulation, but not in MMP-9 mice. Plasma levels and bone marrow concentrations of soluble Kit-ligand (sKitL) were significantly elevated in wild-type mice in response to tissue ischemia, but not in MMP-9 mice. C-kit positive bone marrow cells of MMP-9 mice have attenuated adhesion and migration than those isolated from wild-type mice. In in vitro studies, incubation with selective MMP-9 inhibitor suppressed the colony formation, migration, and tube formation capacities of EPC. Transplantation of bone marrow cells from wild-type mice restored collateral flow formation in MMP-9 mice. CONCLUSIONS-: These findings suggest that MMP-9 deficiency impairs ischemia-induced neovascularization, and these effects may occur through a reduction in releasing the stem cell-active cytokine, and EPC mobilization, migration, and vasculogenesis functions.
Original language | English |
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Pages (from-to) | 1179-1184 |
Number of pages | 6 |
Journal | Arteriosclerosis, Thrombosis, and Vascular Biology |
Volume | 29 |
Issue number | 8 |
DOIs | |
Publication status | Published - Aug 2009 |
Keywords
- Endothelial progenitor cells
- Matrix metalloproteinases
- Neovascularization
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine