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Pericellular proteases in angiogenesis and vasculogenesis

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Author: Hinsbergh, V.W.M. van · Engelse, M.A. · Quax, P.H.A.
Type:article
Date:2006
Institution: TNO Kwaliteit van Leven
Source:Arteriosclerosis, Thrombosis, and Vascular Biology, 4, 26, 716-728
Identifier: 239195
doi: doi:10.1161/01.ATV.0000209518.58252.17
Keywords: Biology · Biomedical Research · Cathepsins · Endothelium · MT-MMPs · Neovascularization · Aminopeptidase · Angiogenic factor · Cathepsin L · Cytokine · Gelatinase A · Gelatinase B · Hemostatic agent · Hermes antigen · Matrix metalloproteinase 14 · Matrix metalloproteinase inhibitor · Pericellular proteinase · Proteinase · Serine proteinase · Unclassified drug · Urokinase · Vitronectin receptor · Accessory cell · Angiogenesis · Antiangiogenic activity · Antigen binding · Blood cell · Bone marrow cell · Cell membrane · Cell migration · Cell survival · Endothelium cell · Enzyme activity · Enzyme localization · Enzyme substrate complex · Extracellular matrix · Focal adhesion · Lamellipodium · Nonhuman · Protein degradation · Receptor binding · Vascular endothelium · ADAM Proteins · Aminopeptidases · Animals · Bone Marrow Cells · Cathepsins · Cell Differentiation · Cell Movement · Extracellular Matrix · Extracellular Matrix Proteins · Humans · Matrix Metalloproteinases · Mice · Neovascularization, Pathologic · Neovascularization, Physiologic · Peptide Hydrolases · Pericytes · Serine Endopeptidases · Tissue Inhibitor of Metalloproteinases

Abstract

Pericellular proteases play an important role in angiogenesis and vasculogenesis. They comprise (membrane-type) matrix metalloproteinases [(MT-)MMPs], serine proteases, cysteine cathepsins, and membrane-bound aminopeptidases. Specific inhibitors regulate them. Major roles in initiating angiogenesis have been attributed to MT1-matrix metalloproteinase (MMP), MMP-2, and MMP-9. Whereas MT-MMPs are membrane-bound by nature, MMP-2 and MMP-9 can localize to the membrane by binding to αvβ3-integrin and CD44, respectively. Proteases switch on neovascularization by activation, liberation, and modification of angiogenic growth factors and degradation of the endothelial and interstitial matrix. They also modify the properties of angiogenic growth factors and cytokines. Neovascularization requires cell migration, which depends on the assembly of protease-protein complexes at the migrating cell front. MT1-MMP and urokinase (u-PA) form multiprotein complexes in the lamellipodia and focal adhesions of migrating cells, facilitating proteolysis and sufficient support for endothelial cell migration and survival. Excessive proteolysis causes loss of endothelial cell-matrix interaction and impairs angiogenesis. MMP-9 and cathepsin L stimulate the recruitment and action of blood- or bone-marrow-derived accessory cells that enhance angiogenesis. Proteases also generate fragments of extracellular matrix and hemostasis factors that have anti-angiogenic properties. Understanding the complexity of protease activities in angiogenesis contributes to recognizing new targets for stimulation or inhibition of neovascularization in disease. © 2006 American Heart Association, Inc. Chemicals / CAS: aminopeptidase, 9031-94-1; cathepsin L, 60616-82-2; cathepsin, 9004-08-4; gelatinase A, 146480-35-5; gelatinase B, 146480-36-6; proteinase, 9001-92-7; serine proteinase, 37259-58-8; urokinase, 139639-24-0; ADAM Proteins, EC 3.4.24.-; Aminopeptidases, EC 3.4.11.-; Cathepsins, EC 3.4.-; Extracellular Matrix Proteins; Matrix Metalloproteinases, EC 3.4.24.-; Peptide Hydrolases, EC 3.4.-; Serine Endopeptidases, EC 3.4.21.-; Tissue Inhibitor of Metalloproteinases