reviewTop 1% cited

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

Arteriosclerosis Thrombosis and Vascular Biology · 2001 · Vol. 21(7) · pp. 1104–1117

Michael S. Pepper✉(Morpho (United States))

Abstract

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.

Protease and Inhibitor Mechanisms Blood Coagulation and Thrombosis Mechanisms Peptidase Inhibition and AnalysisAngiogenesisPlasminMatrix metalloproteinasePlasminogen activatorNeovascularizationExtracellular matrixUrokinase receptorUrokinaseVitronectinCancer research

MeSH terms

AnimalsExtracellular MatrixFibrinolysinFibrinolysisMetalloendopeptidasesNeoplasmsNeovascularization, PathologicTissue Plasminogen ActivatorPlasminogen ActivatorsReceptors, Cell SurfaceUrokinase-Type Plasminogen ActivatorPlasminogen Activator Inhibitor 1Matrix MetalloproteinasesMatrix Metalloproteinases, Membrane-AssociatedReceptors, Urokinase Plasminogen Activator