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Abstract

Tissue inhibitor of metalloproteinases-3 (TIMP3) is one of four members of a family of proteins that were originally classified according to their ability to inhibit matrix metalloproteinases (MMP). TIMP3, which encodes a potent angiogenesis inhibitor, is mutated in Sorsby fundus dystrophy, a macular degenerative disease with submacular choroidal neovascularization. In this study we demonstrate the ability of TIMP3 to inhibit vascular endothelial factor (VEGF)-mediated angiogenesis and identify the potential mechanism by which this occurs: TIMP3 blocks the binding of VEGF to VEGF receptor-2 and inhibits downstream signaling and angiogenesis. This property seems to be independent of its MMP-inhibitory activity, indicating a new function for this molecule.

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PubMed ID:: 12652295

DOI:: 10.1038/nm846

ScienceOpen disciplines: Chemistry

Keywords: Cell Division,drug effects,Cell Line,Endothelial Growth Factors,metabolism,pharmacology,Endothelium,cytology,Humans,Intercellular Signaling Peptides and Proteins,Lymphokines,Neovascularization, Pathologic,prevention & control,Neuropilins,Phosphorylation,Receptors, Vascular Endothelial Growth Factor,Recombinant Proteins,Tissue Inhibitor of Metalloproteinase-3,Tissue Inhibitor of Metalloproteinases,genetics,physiology,Vascular Endothelial Growth Factor A,Vascular Endothelial Growth Factors

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