Matrix Metalloproteinases: New Routes to the Use of MT1-MMP As A Therapeutic Target in Angiogenesis-Related Disease

Author(s): A. G. Arroyo, L. Genis, P. Gonzalo, S. Matias-Roman, A. Pollan, B. G. Galvez

Journal Name: Current Pharmaceutical Design

Volume 13 , Issue 17 , 2007

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Angiogenesis, the formation of new vessels from pre-existing capillaries, is a fundamental physiological process which is also critical for the development of several pathological conditions; thus a diminished angiogenic response is related to ischemic disorders, whereas increased angiogenesis is associated with tumorigenesis and chronic inflammatory diseases. New ways of modulating angiogenesis therefore have potential in the treatment of these diseases. During angiogenesis, normally quiescent endothelial cells (ECs) become migratory and invade the surrounding tissue. To do this, they require a specific enzyme machinery to degrade the tissue barriers presented by the basement membranes and the interstitial matrix. This function is supplied by matrix metalloproteinase (MMP) proteins, a large family of enzymes responsible for degrading a variety of extracellular matrix (ECM) components and for modulating the bioactivity of transmembrane receptors and soluble factors. In this review we examine the participation of MMPs - in particular membrane type 1-matrix metalloproteinase (MT1-MMP) - in the different steps of angiogenesis, and discuss the mechanisms of regulation of MT1-MMP in ECs. Finally, we explore the potential use of MMP inhibitors (MMPI) in the treatment of angiogenesis-related disease, with especial emphasis on novel approaches to the inhibition of MT1-MMP activity in ECs.

Keywords: Matrix remodelling, MT1-MMP, endothelial cells, angiogenesis, inflammation, therapy

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Article Details

Year: 2007
Page: [1787 - 1802]
Pages: 16
DOI: 10.2174/138161207780831284
Price: $65

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