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Q. Ebrahem, B.A. Apte; VEGF Induction of Corneal Neovascularization is Mediated by Matrix Metalloproteinases . Invest. Ophthalmol. Vis. Sci. 2006;47(13):2601.
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Matrix metalloproteinases (MMPs) are a specialized group of enzymes that participate in extracellular matrix (ECM) degradation and have been postulated to play an important role in angiogenesis. The purpose of this study was to determine if the MMPs were involved upstream or downstream of VEGF in vivo.
Hydron micropellets containing pro form or active form of MMPs (MMP–2 and MMP–9) were placed in micropockets in rat corneas and analyzed one week after implantation for their ability to induce a neovascular response. The ability of MMP inhibitors and VEGF neutralizing antibodies to inhibit the MMP as well as a VEGF mediated response was examined. In situ zymograms to determine the localization of MMPs following VEGF stimulation was analyzed in endothelial cells.
Active MMPs initiate an angiogenic response in the rat corneal assay in the form of growth of new vessels towards MMP loaded pellets. In addition, synthetic inhibitor of MMPs can inhibit the angiogenic response of VEGF.
Active MMPs can initiate an angiogenic response that is mediated by release of low levels of VEGF. Our data suggests that MMPs may act upstream as well as downstream of VEGF during in vivo angiogenesis.
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