Arteriosclerosis, Thrombosis, and Vascular Biology. 2001;21:1104-1117
doi: 10.1161/hq0701.093685
doi: 10.1161/hq0701.093685
© 2001 American Heart Association, Inc.
Brief Review |
Role of the Matrix Metalloproteinase and Plasminogen Activator–Plasmin Systems in Angiogenesis
From the Department of Morphology, University Medical Center, Geneva, Switzerland.
Correspondence to Dr M.S. Pepper, Département de Morphologie, Centre Médical Universitaire, 1, rue Michel-Servet, 1211 Genève 4, Switzerland. E-mail: michael.pepper{at}medecine.unige.ch
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.
Key Words: extracellular matrix • endothelium • metalloproteinase • plasminogen • cancer
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 T. Koike, R. B. Vernon, M. D. Gooden, E. Sadoun, and M. J. Reed Inhibited Angiogenesis in Aging: A Role for TIMP-2 J. Gerontol. A Biol. Sci. Med. Sci., September 1, 2003; 58(9): B798 - 805. [Abstract] [Full Text] [PDF]
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J. Sturge, D. Wienke, L. East, G. E. Jones, and C. M. Isacke GPI-anchored uPAR requires Endo180 for rapid directional sensing during chemotaxis J. Cell Biol., September 1, 2003; 162(5): 789 - 794. [Abstract] [Full Text] [PDF]
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M. Buchholz, A. Biebl, A. Neesse, M. Wagner, T. Iwamura, G. Leder, G. Adler, and T. M. Gress SERPINE2 (Protease Nexin I) Promotes Extracellular Matrix Production and Local Invasion of Pancreatic Tumors in Vivo Cancer Res., August 15, 2003; 63(16): 4945 - 4951. [Abstract] [Full Text] [PDF]
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M. L. Ponce, S. Hibino, A. M. Lebioda, M. Mochizuki, M. Nomizu, and H. K. Kleinman Identification of a Potent Peptide Antagonist to an Active Laminin-1 Sequence That Blocks Angiogenesis and Tumor Growth Cancer Res., August 15, 2003; 63(16): 5060 - 5064. [Abstract] [Full Text] [PDF]
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S. Chuang-Tsai, T. H. Sisson, N. Hattori, C. G. Tsai, N. M. Subbotina, K. E. Hanson, and R. H. Simon Reduction in Fibrotic Tissue Formation in Mice Genetically Deficient in Plasminogen Activator Inhibitor-1 Am. J. Pathol., August 1, 2003; 163(2): 445 - 452. [Abstract] [Full Text] [PDF]
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M. L. Cher, H. R. Biliran Jr., S. Bhagat, Y. Meng, M. Che, J. Lockett, J. Abrams, R. Fridman, M. Zachareas, and S. Sheng Maspin expression inhibits osteolysis, tumor growth, and angiogenesis in a model of prostate cancer bone metastasis PNAS, June 24, 2003; 100(13): 7847 - 7852. [Abstract] [Full Text] [PDF]
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K. Kallenbach, H. A. Fernandez, G. Seghezzi, F. G. Baumann, S. Patel, E. A. Grossi, A. C. Galloway, and P. Mignatti A Quantitative In Vitro Model of Smooth Muscle Cell Migration Through the Arterial Wall Using the Human Amniotic Membrane Arterioscler Thromb Vasc Biol, June 1, 2003; 23(6): 1008 - 1013. [Abstract] [Full Text] [PDF]
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J.-M. Rakic, V. Lambert, C. Munaut, K. Bajou, K. Peyrollier, M.-L. Alvarez-Gonzalez, P. Carmeliet, J.-M. Foidart, and A. Noel Mice without uPA, tPA, or Plasminogen Genes Are Resistant to Experimental Choroidal Neovascularization Invest. Ophthalmol. Vis. Sci., April 1, 2003; 44(4): 1732 - 1739. [Abstract] [Full Text] [PDF]
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 P. E. Rakoczy, M. Brankov, A. Fonceca, T. Zaknich, B. C. Rae, and C.-M. Lai Enhanced Recombinant Adeno-Associated Virus-Mediated Vascular Endothelial Growth Factor Expression in the Adult Mouse Retina: A Potential Model for Diabetic Retinopathy Diabetes, March 1, 2003; 52(3): 857 - 863. [Abstract] [Full Text] [PDF]
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 P.O Bonetti, L.O Lerman, C Napoli, and A Lerman Statin effects beyond lipid lowering--are they clinically relevant? Eur. Heart J., February 1, 2003; 24(3): 225 - 248. [Full Text] [PDF]
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L. Berglin, S. Sarman, I. van der Ploeg, B. Steen, Y. Ming, S. Itohara, S. Seregard, and A. Kvanta Reduced Choroidal Neovascular Membrane Formation in Matrix Metalloproteinase-2-Deficient Mice Invest. Ophthalmol. Vis. Sci., January 1, 2003; 44(1): 403 - 408. [Abstract] [Full Text] [PDF]
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V. Lambert, C. Munaut, M. Jost, A. Noel, Z. Werb, J.-M. Foidart, and J.-M. Rakic Matrix Metalloproteinase-9 Contributes to Choroidal Neovascularization Am. J. Pathol., October 1, 2002; 161(4): 1247 - 1253. [Abstract] [Full Text] [PDF]
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J. C. Juarez, X. Guan, N. V. Shipulina, M. L. Plunkett, G. C. Parry, D. E. Shaw, J.-C. Zhang, S. A. Rabbani, K. R. McCrae, A. P. Mazar, et al. Histidine-Proline-rich Glycoprotein Has Potent Antiangiogenic Activity Mediated through the Histidine-Proline-rich Domain Cancer Res., September 15, 2002; 62(18): 5344 - 5350. [Abstract] [Full Text] [PDF]
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U. R. Pendurthi, M. Ngyuen, P. Andrade-Gordon, L. C. Petersen, and L. V. M. Rao Plasmin Induces Cyr61 Gene Expression in Fibroblasts Via Protease-Activated Receptor-1 and p44/42 Mitogen-Activated Protein Kinase-Dependent Signaling Pathway Arterioscler Thromb Vasc Biol, September 1, 2002; 22(9): 1421 - 1426. [Abstract] [Full Text] [PDF]
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S. Sakurai, S. Alam, G. Pagan-Mercado, F. Hickman, J.-Y. Tsai, P. Zelenka, and S. Sato Retinal Capillary Pericyte Proliferation and c-Fos mRNA Induction by Prostaglandin D2 through the cAMP Response Element Invest. Ophthalmol. Vis. Sci., August 1, 2002; 43(8): 2774 - 2781. [Abstract] [Full Text] [PDF]
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 A. R. Farina, M.-P. Masciulli, A. Tacconelli, L. Cappabianca, G. De Santis, A. Gulino, and A. R. Mackay All-trans-Retinoic Acid Induces Nuclear Factor {kappa}B Activation and Matrix Metalloproteinase-9 Expression and Enhances Basement Membrane Invasivity of Differentiation-resistant Human SK-N-BE 9N Neuroblastoma Cells Cell Growth Differ., August 1, 2002; 13(8): 343 - 354. [Abstract] [Full Text] [PDF]
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A. G. Polson, D. Wang, J. DeRisi, and D. Ganem Modulation of Host Gene Expression by the Constitutively Active G Protein-coupled Receptor of Kaposi's Sarcoma-associated Herpesvirus Cancer Res., August 1, 2002; 62(15): 4525 - 4530. [Abstract] [Full Text] [PDF]
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B. H. Rauch, E. Bretschneider, M. Braun, and K. Schror Factor Xa Releases Matrix Metalloproteinase-2 (MMP-2) From Human Vascular Smooth Muscle Cells and Stimulates the Conversion of Pro-MMP-2 to MMP-2: Role of MMP-2 in Factor Xa-Induced DNA Synthesis and Matrix Invasion Circ. Res., May 31, 2002; 90(10): 1122 - 1127. [Abstract] [Full Text] [PDF]
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