Role of the Matrix Metalloproteinase and Plasminogen Activator–Plasmin Systems in Angiogenesis

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  • Michael S. Pepper
    From the Department of Morphology, University Medical Center, Geneva, Switzerland.

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<jats:p><jats:italic>Abstract</jats:italic>—Extracellular proteolysis is an absolute requirement for new blood vessel formation (angiogenesis). This review examines the role of the matrix metalloproteinase (MMP) and plasminogen activator (PA)–plasmin systems during angiogenesis. Specifically, a role for gelatinases (MMP-2, MMP-9), membrane-type 1 MMP (MMP-14), the urokinase-type PA receptor, and PA inhibitor 1 has been clearly defined in a number of model systems. The MMP and PA-plasmin systems have also been implicated in experimental vascular tumor formation, and their role during this process will be examined. Antiproteolysis, particularly in the context of angiogenesis, has become a key target in therapeutic strategies aimed at inhibiting tumor growth and other diseases associated with neovascularization.</jats:p>

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