Matrix Metalloproteinase System Deficiencies and Matrix Degradation

Introduction

Matrix metalloproteinases (MMPs) constitute a tightly regulated family of enzymes that degrade most components of the extracellular matrix. They are classified based on substrate specificity. Collagenases (MMP-1, interstitial collagenase, EC 3.4.24.7; MMP-8, neutrophil collagenase, EC 3.4.24.34; MMP-13, collagenase-3) degrade connective tissue collagens. Gelatinases (MMP-2, gelatinase A, EC 3.4.24.24; MMP-9, gelatinase B, EC 3.4.24.35) degrade collagen types IV, V, VII and X, elastin, and denatured collagens. Stromelysins (MMP-3, stromelysin-1, EC 3.4.24.17; MMP-10, stromelysin-2, EC 3.4.24.22) and matrilysin (MMP-7, EC 3.4.24.23) degrade the proteoglycan core proteins, laminin, fibronectin, elastin, gelatin, and nonhelical collagen, whereas stromelysin-3 (MMP-11) does not degrade any of the major extracellular matrix components. Macrophage metalloelastase (MMP-12, EC 3.4.24.65) degrades insoluble elastin, collagen IV, fibronectin, laminin, entactin, and proteoglycans.^1-7 About 20 members of the MMP family have been identified, including at least four membrane-type (MT) MMPs.^8-13

MMPs are generally secreted as zymogens that are extracellularly activated by organomercurial compounds, several proteinases (including plasmin, trypsin, chymotrypsin, kallikrein, cathepsin G, or neutrophil elastase), oxygen free radicals, or by association with the cell surface.^1,5,6 Active MMPs are inhibited by specific tissue inhibitors of MMPs (TIMPs) via formation of a noncovalent stoichiometric complex.^5,6 Four members of the TIMP family have been identified, of which TIMP-1, synthesized by most types of connective tissue cells and by macrophages, acts against all members of the collagenase, stromelysin, and gelatinase classes.^2,14,15

MMPs are mainly involved in the degradation of extracellular matrix components, but may also play a role in activation and processing of cytokines or growth factors,¹⁶ in shedding of membrane-bound receptors,¹⁷ in liberation of Fas ligand,¹⁸ or in activation of tumor necrosis factor-α.¹⁹ Degradation of extracellular matrix is required to allow cell migration and tissue remodeling, which play essential roles in many (patho)physiological processes. The role of the plasminogen/plasmin (fibrinolytic) and MMP systems in neointima formation after vascular injury, atherosclerosis, graft arterial disease, myocardial ischemia, angiogenesis, tumor growth and dissemination, infection, and chronic inflammatory disorders of the kidney, lung, gastrointestinal tract, skin, joints, or cornea has recently been reviewed.²⁰ We will discuss some recent data on interactions between the MMP and plasminogen/plasmin systems and their role in neointima formation and atherosclerotic aneurysm formation.

• References

• 1 Murphy G. Matrix metalloproteinases and their inhibitors. Acta Orthop Scand 1995; 66 (Suppl. 256) 55-60.
• 2 Dollery CM, McEwan JR, Henney AM. Matrix metalloproteinases and cardiovascular disease. Circ Res 1995; 77: 863-868.
• 3 Mignatti P, Rifkin DB. Plasminogen activators and matrix metalloproteinases in angiogenesis. Enzyme Protein 1996; 49: 117-137.
• 4 Matrisian LM. Metalloproteinases and their inhibitors in matrix remodeling. Trends Genet 1990; 6: 121-125.
• 5 Woessner Jr JF. Matrix metalloproteinases and their inhibitors in connective tissue remodeling. FASEB J 1991; 5: 2145-2154.
• 6 Birkedal-Hansen H. Proteolytic remodeling of extracellular matrix. Curr Opin Cell Biol 1995; 7: 728-735.
• 7 Coussens LM, Werb Z. Matrix metalloproteinases and the development of cancer. Chem Biol 1996; 3: 895-904.
• 8 Jenkins GM, Crow MT, Bilato C, Gluzband Y, Ryu WS, Li Z, Stetler-Stevenson W, Nater C, Froehlich JP, Lakatta EG, Gheng L. Increased expression of membrane-type matrix metalloproteinase and preferential localization of matrix metalloproteinase-2 to the neointima of balloon-injured rat carotid arteries. Circulation 1998; 97: 82-90.
• 9 Sato H, Okada Y, Seiki M. Membrane-type matrix metalloproteinases (MT-MMPs) in cell invasion. Thromb Haemost 1997; 78: 497-500.
• 10 Apte SS, Fukai N, Beier DR, Olsen BR. The matrix metalloproteinase-14 (MMP-14) gene is structurally distinct from other MMP genes and is co-expressed with the TIMP-2 gene during mouse embryogenesis. J Biol Chem 1997; 272: 25511-25517.
• 11 Mattei MG, Roeckel N, Olsen BR, Apte SS. Genes of the membrane-type matrix metalloproteinase (MT-MMP) gene family, MMP14, MMP15, and MMP16, localize to human chromosomes 14, 16, and 8, respectively. Genomics 1997; 40: 168-169.
• 12 Llano E, Pendas AM, Knauper V, Sorsa T, Salo T, Salido E, Murphy G, Simmer JP, Barlett JD, Lopez-Otin C. Identification and structural and functional characterization of human enamylysin (MMP-20). Biochemistry 1997; 36: 15101-15108.
• 13 Sedlacek R, Mauch S, Kolb B, Schatzlein C, Eibel H, Peter HH, Schmitt J, Krawinkel U. Matrix metalloproteinase MMP-19 (RASI-1) is expressed on the surface of activated peripheral blood mononuclear cells and is detected as an autoantigen in rheumatoid arthritis. Immunobiology 1998; 198: 408-423.
• 14 Leco KJ, Apte SS, Taniguchi GT, Hawkes SP, Khokha R, Schultz GA, Edwards DR. Murine tissue inhibitor of metalloproteinases-4 (TIMP-4) - cDNA isolation and expression in adult mouse tissues. FEBS Lett 1997; 401: 213-217.
• 15 Greene J, Wang MS, Liu YLE, Raymond LA, Rosen C, Shi YNE. Molecular cloning and characterization of human tissue inhibitor of metalloproteinase 4. J Biol Chem 1996; 271: 30375-30380.
• 16 Suzuki M, Raab G, Moses MA, Fernandez CA, Klagsbrun M. Matrix metalloproteinase-3 releases active heparin-binding EGF-like growth factor by cleavage at a specific juxtamembrane site. J Biol Chem 1997; 272: 31730-31737.
• 17 Preece G, Murphy G, Ager A. Metalloproteinase-mediated regulation of L-selectin levels of leukocytes. J Biol Chem 1996; 271: 11634-11640.
• 18 Kayagaki N, Kawasaki A, Ebata T, Ohmoto H, Ikeda S, Inoue S, Yoshino K, Okumura K, Yagita H. Metalloproteinase-mediated release of human Fas ligand. J Exp Med 1996; 182: 1777-1783.
• 19 Black RA, Rauch CT, Kozlosky C, Peshon JJ, Slack JL, Wolfson MF, Castner BJ, Stocking KL, Reddy P, Srinivasan S, Nelson N, Boiani N, Schooley KA, Gerhart M, Davis R, Fitzner JN, Johnson RS, Paxton RJ, March CJ, Ceretti DP. A metalloproteinase disintegrin that releases tumor-necrosis factor-alpha from cells. Nature 1997; 385: 729-733.
• 20 Carmeliet P, Collen D. Development and disease in proteinase-deficient mice: role of the plasminogen, matrix metalloproteinase and coagulation system. Thromb Res 1998; 91: 255-285.
• 21 Van Leeuwen RTJ. Extracellular proteolysis and the migrating vascular smooth muscle cell. Fibrinolysis 1996; 10: 59-74.
• 22 Lijnen HR, Collen D. Mechanisms of physiological fibrinolysis. Baillières Clinical Haematology 1995; 8: 277-290.
• 23 Okada Y, Gonoji Y, Naka K, Tomita K, Nakanishi I, Iwata K, Yamashita K, Hayakawa T. Matrix metalloproteinase 9 (92-kDa gelatinase/type IV collagenase) from HT 1080 human fibrosarcoma cells: purification and activation of the precursor and enzymic properties. J Biol Chem 1992; 267: 21712-21719.
• 24 Suzuki K, Enghild JJ, Morodomi T, Salvesen G, Nagase H. Mechanisms of activation of tissue procollagenase by matrix metalloproteinase 3 (stromelysin). Biochemistry 1990; 29: 10261-10270.
• 25 Murphy G, Cockett MI, Stephens PE, Smith BJ, Docherty AJ. Stromelysin is an activator of procollagenase: a study with natural and recombinant enzymes. Biochem J 1987; 248: 265-268.
• 26 Ogata Y, Enghild JJ, Nagase H. Matrix metalloproteinase 3 (stromelysin) activates the precursor for the human matrix metalloproteinase 9. J Biol Chem 1992; 267: 3581-3584.
• 27 Imai K, Yokohama Y, Nakanishi I, Ohuchi E, Fujii Y, Nakai N, Okada Y. Matrix metalloproteinase 7 (matrilysin) from human rectal carcinoma cells: activation of the precursor, interaction with other matrix metalloproteinases and enzymic properties. J Biol Chem 1995; 270: 6691-6697.
• 28 Knauper P, Smith B, Lopez Otin C, Murphy G. Activation of progelatinase B (pro-MMP-9) by active collagenase-3 (MMP-13). Eur J Biochem 1997; 248: 369-373.
• 29 Eeckhout Y, Vaes G. Further studies on the activation of procollagenase, the latent precursor of bone collagenase: effects of lysosomal cathepsin B, plasmin and kallikrein, and spontaneous activation. Biochem J 1977; 166: 21-31.
• 30 He CS, Wilhelm SM, Pentland AP, Marmer BL, Grant GA, Eisen AZ, Goldberg GI. Tissue cooperation in a proteolytic cascade activating human interstitial collagenase. Proc Natl Acad Sci USA 1989; 86: 2632-2636.
• 31 Murphy G, Atkinson S, Ward R, Gavrilovic J, Reynolds JJ. The role of plasminogen activators in the regulation of connective tissue metalloproteinases. Ann NY Acad Sci 1992; 667: 1-12.
• 32 Murphy G, Ward R, Hembry RM, Reynolds JJ, Kuhn K, Tryggvason K. Characterization of gelatinase from pig polymorphonuclear leucocytes: a metalloproteinase resembling tumour type IV collagenase. Biochem J 1989; 258: 463-472.
• 33 Lyons JG, Birkedal-Hansen B, Moore WGI, O’Grady RL, Birkedal-Hansen H. Characteristics of a 95-kDa matrix metalloproteinase produced by mammary carcinoma cells. Biochemistry 1991; 30: 1449-1456.
• 34 Okada Y, Morodomi T, Enghild JJ, Suzuki K, Yasui A, Nakanishi I, Salvesen G, Nagase H. Matrix metalloproteinase 2 from human rheumatoid synovial fibroblasts: purification and activation of the precursor and enzymatic properties. Eur J Biochem 1990; 194: 721-730.
• 35 Chen JM, Aimes RT, Ward GR, Youngleib GL, Quigley JP. Isolation and characterization of a 70-kDa metalloprotease (gelatinase) that is elevated in Rous sarcoma virus-transformed chicken embryo fibroblasts. J Biol Chem 1991; 266: 5113-5121.
• 36 Mazzieri R, Masiero L, Zanetta L, Monea S, Onisto M, Garbisa S, Mignatti P. Control of type IV collagenase activity by components of the urokinase-plasmin system: a regulatory mechanism with cell-bound reactants. EMBO J 1997; 16: 2319-2332.
• 37 Baramova EN, Bajou K, Remacle A, L’Hoir C, Krell HW, Weidle UH, Noel A, Foidart JM. Involvement of PA/plasmin system in the processing of proMMP-9 and in the second step of proMMP-2 activation. FEBS Lett 1997; 405: 157-162.
• 38 Keski-Oja J, Lohi J, Tuuttila A, Tryggvason K, Vartio T. Proteolytic processing of the 72,000-Da Type IV collagenase by urokinase plasminogen activation. Exp Cell Res 1992; 202: 471-476.
• 39 Moll UM, Youngleib GL, Rosinski KB, Quigley JP. Tumor promoter-stimulated Mr 92,000 gelatinase secreted by normal and malignant human cells: isolation and characterization of the enzyme from HT1080 tumor cells. Cancer Res 1990; 50: 6162-6170.
• 40 Mignatti P, Robbins E, Rifkin DB. Tumor invasion through the human amniotic membrane: requirement for a proteinase cascade. Cell 1986; 47: 487-498.
• 41 Reich R, Thompson EW, Iwamoto Y, Martin GR, Deason JR, Fuller GC, Miskin R. Effects of inhibitors of plasminogen activator, serine proteinases, and collagenase IV on the invasion of basement membranes by metastatic cells. Cancer Res 1988; 48: 3307-3312.
• 42 Lijnen HR, Silence J, Lemmens G, Frederix L, Collen D. Regulation of gelatinase activity in mice with targeted inactivation of components of the plasminogen/plasmin system. Thromb Haemost 1998; 79: 1171-1176.
• 43 Lijnen HR, Van Hoef B, Lupu F, Moons L, Carmeliet P, Collen D. Function of the plasminogen/plasmin and matrix metalloproteinase systems after vascular injury in mice with targeted inactivation of fibrinolytic system genes. Arterioscler Thromb Vasc Biol 1998; 18: 1035-1045.
• 44 Lijnen HR, Silence J, Van Hoef B, Collen D. Stromelysin-1 (MMP-3)-independent gelatinase expression and activation in mice. Blood 1998; 91: 2045-2053.
• 45 Bini A, Itoh Y, Kudryk BJ, Nagase H. Degradation of cross-linked fibrin by matrix metalloproteinase 3 (stromelysin 1): hydrolysis of the Gly404-Ala405 peptide bond. Biochemistry 1996; 35: 13056-13063.
• 46 Marcotte PA, Kozan IM, Dorwin SA, Ryan JM. The matrix metalloproteinase Pump-1 catalyses formation of low molecular weight (pro)urokinase in cultures of normal human kidney cells. J Biol Chem 1992; 267: 13803-13806.
• 47 Ugwu F, Van Hoef B, Bini A, Collen D, Lijnen HR. Proteolytic cleavage of urokinase-type plasminogen activator by stromelysin-1 (MMP-3). Biochemistry 1998; 37: 7231-7236.
• 48 Carmeliet P, Moons L, Dewerchin M, Rosenberg S, Herbert JM, Lupu F, Collen D. Receptor-independent role of urokinase-type plasminogen activator in arterial wound healing and intima formation in mice. J Cell Biol 1998; 140: 233-245.
• 49 Lijnen HR, Ugwu F, Bini A, Collen D. Generation of an angiostatin-like fragment from plasminogen by stromelysin-1 (MMP-3). Biochemistry 1998; 37: 4699-4702.
• 50 O’Reilly MS, Holmgren L, Shing Y, Chen C, Rosenthal RA, Moses M, Lane WS, Cao Y, Sage EH, Folkman J. Angiostatin: a novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma. Cell 1994; 79: 315-328.
• 51 Cao Y, Ji RW, Davidson D, Schaller J, Marti D, Söhndel S, McCance SG, O’Reilly MS, Llinas M, Folkman J. Kringle domains of human angiostatin: characterization of the anti-proliferative activity on endothelial cells. J Biol Chem 1996; 271: 29461-29467.
• 52 Dong Z, Kumar R, Yang X, Fidler IJ. Macrophage-derived metalloelastase is responsible for the generation of angiostatin in Lewis lung carcinoma. Cell 1997; 88: 801-810.
• 53 Gately S, Twardowski P, Stack MS, Patrick M, Boggio L, Cundiff DL, Schnaper HW, Madison L, Volpert O, Bouck N, Enghild J, Kwaan HC, Soff GA. Human prostate carcinoma cells express enzymatic activity that converts human plasminogen to the angiogenesis inhibitor, angiostatin. Cancer Res 1996; 56: 4887-4890.
• 54 Gately S, Twardowski P, Stack MS, Cundiff DL, Grella D, Castellino FJ, Enghild J, Kwaan HC, Lee F, Kramer RA, Volpert O, Bouck N, Soff GA. The mechanism of cancer-mediated conversion of plasminogen to the angiogenesis inhibitor angiostatin. Proc Natl Acad Sci USA 1997; 94: 10868-10872.
• 55 Stathakis P, Fitzgerald M, Matthias LJ, Chesterman CN, Hogg PJ. Generation of angiostatin by reduction and proteolysis of plasmin: catalysis by a plasmin reductase secreted by cultured cells. J Biol Chem 1997; 272: 20641-20645.
• 56 Patterson BC, Sang QA. Angiostatin-converting enzyme activities of human matrilysin (MMP-7) and gelatinase B/type IV collagenase (MMP-9). J Biol Chem 1997; 272: 28823-28825.
• 57 Davidson DJ, Reininger I, Ennis BW, Quan N, Haskell C, Wang J, Henkin J. Sixth International Workshop on the Molecular and Cellular Biology of Plasminogen Activation. San Diego; (Abstract 200) 1997
• 58 Lijnen HR, Van Hoef B, Soloway P, Collen D. Plasminogen/plasmin system function in mice deficient in stromelysin-1 (MMP-3) or in tissue inhibitor of metalloproteinases type 1 (TIMP-1). Fibrinolysis & Proteolysis 1998; 12: 1-8.
• 59 Lijnen HR, Ugwu F, Rio MC, Collen D. Plasminogen/plasmin and matrix metalloproteinase system function in mice with targeted inactivation of stromelysin-3 (MMP-11). Fibrinolysis & Proteolysis 1998; 12: 155-164.
• 60 Murphy G, Segain J-P, O’Shea M, Cockett M, Iannou C, Lefebvre O, Chambon P, Basset P. The 28-kDa N-terminal domain of mouse stromelysin-3 has the general properties of a weak metalloproteinase. J Biol Chem 1993; 269: 15435-15441.
• 61 Noël A, Santavicca M, Stoll I, L’Hoir C, Staub A, Murphy G, Rio M-C, Basset P. Identification of structural determinants controlling human and mouse stromelysin-3 proteolytic activities. J Biol Chem 1995; 270: 22866-22872.
• 62 Libby P, Schwartz D, Brogi E, Tanaka H, Clinton SK. A cascade model for restenosis: a special case of atherosclerosis progression. Circulation 1992; 86: 47-52.
• 63 Clowes AW, Reidy MA. Prevention of stenosis after vascular reconstruction: pharmacologic control of intimal hyperplasia: a review. J Vasc Surg 1991; 13: 885-891.
• 64 Schwartz SM, Reidy MA, O’Brien ER. Assessment of factors important in atherosclerotic occlusion and restenosis. Thromb Haemost 1995; 74: 541-551.
• 65 Kakuta T, Currier JW, Haudenschild CC, Ryan TJ, Faxon DP. Differences in compensatory vessel enlargement, not intimal formation, account for restenosis after angioplasty in the hypercholesterolemic rabbit model. Circulation 1994; 89: 2809-2815.
• 66 Carmeliet P, Moons L, Stassen JM, De Mol M, Bouché A, van den Oord JJ, Kockx M, Collen D. Vascular wound healing and neointima formation induced by perivascular electric injury in mice. Am J Pathol 1997; 150: 761-776.
• 67 Celentano DC, Frishman WH. Matrix metalloproteinases and coronary artery disease: a novel therapeutic target. J Clin Pharmacol 1997; 37: 991-1000.
• 68 Newman KM, Jean Claude J, Li H, Scholes JV, Ogata Y, Nagase H, Tilson MD. Cellular localization of matrix metalloproteinase in the abdominal aortic aneurysm wall. J Vasc Surg 1994; 20: 814-820.
• 69 Galis ZS, Sukhova GK, Kranzhöfer R, Clark S, Libby P. Macrophage foam cells from experimental atheroma constitutively produce matrix-degrading proteinases. Proc Natl Acad Sci USA 1995; 92: 402-406.
• 70 Galis ZS, Muszynski M, Sukhova GK, Simon Morrissey E, Unemori EN, Lark MW, Amento E, Libby P. Cytokine-stimulated human vascular smooth muscle cells synthesize a complement of enzymes required for extracellular matrix digestion. Circ Res 1994; 75: 181-189.
• 71 Halpert I, Sires UI, Roby JD, Potter Perigo S, Wight TN, Shapiro SD, Welgus HG, Wickline SA, Parks WC. Matrilysin is expressed by lipid-laden macrophages at sites of potential rupture in atherosclerotic lesions and localizes to areas of versican deposition, a proteoglycan substrate for the enzyme. Proc Natl Acad Sci USA 1996; 93: 9748-9753.
• 72 Irizarry E, Newman KM, Gandhi RH, Nackman GB, Halpern V, Wishner S, Scholes JV, Tilson MD. Demonstration of interstitial collagenase in abdominal aortic aneurysm disease. J Surg Res 1993; 54: 571-574.
• 73 Sakalihasan N, Delvenne P, Nusgens BV, Limet R, Lapiere CM. Activated forms of MMP2 and MMP9 in abdominal aortic aneurysms. J Vasc Surg 1996; 24: 127-133.
• 74 Moons L, Shi V, Ploplis V, Plow E, Haber E, Collen D, Carmeliet P. Reduced transplant arteriosclerosis in plasminogen deficient mice. J Clin Invest. In press.
• 75 Clowes AW, Clowes MM, Au YP, Reidy MA, Belin D. Smooth muscle cells express urokinase during mitogenesis and tissue-type plasminogen activator during migration in injured rat carotid artery. Circ Res 1990; 67: 61-67.
• 76 Jackson CL, Reidy MA. The role of plasminogen activation in smooth muscle cell migration after arterial injury. Ann NY Acad Sci 1992; 667: 141-150.
• 77 Reidy MA, Irvin C, Lindner V. Migration of arterial wall cells: expression of plasminogen activators and inhibitors in injured rat arteries. Circ Res 1996; 78: 405-414.
• 78 Bendeck MP, Zempo N, Clowes AW, Galardy RE, Reidy MA. Smooth muscle cell migration and matrix metalloproteinase expression after arterial injury in the rat. Circ Res 1994; 75: 539-545.
• 79 Zempo N, Kenagy RD, Au YPT, Bendeck M, Clowes MM, Reidy MA, Clowes AW. Matrix metalloproteinases of vascular cells are increased in balloon-injured rat carotid artery. J Vasc Surg 1994; 20: 209-217.
• 80 Hasenstab D, Forough R, Clowes AW. Plasminogen activator inhibitor type 1 and tissue inhibitor of metalloproteinases-2 increase after arterial injury in rats. Circ Res 1997; 80: 490-496.
• 81 Zempo N, Koyama N, Kenagy RD, Lea HJ, Clowes AW. Regulation of vascular smooth muscle cell migration and proliferation in vitro and in injured rat arteries by a synthetic matrix metalloproteinase inhibitor. Arterioscler Thromb Vasc Biol 1996; 16: 28-33.
• 82 Forough R, Koyama N, Hasenstab D, Lea H, Clowes M, Nikkari ST, Clowes AW. Overexpression of tissue inhibitor of matrix metalloproteinase-1 inhibits vascular smooth muscle cell functions in vitro and in vivo. Circ Res 1996; 79: 812-820.
• 83 George SJ, Johnson JL, Angelini GD, Newby AC, Baker AH. Adenovirus-mediated gene transfer of the human TIMP-1 gene inhibits smooth muscle cell migration and neointimal formation in human saphenous vein. Hum Gene Ther 1998; 9: 867-877.
• 84 Kenagy RD, Hart CE, Stetler-Stevenson WG, Clowes AW. Primate smooth muscle cell migration from aortic explants is mediated by endogenous platelet-derived growth factor and basic fibroblast growth factor acting through matrix metalloproteinases 2 and 9. Circulation 1997; 96: 3555-3560.
• 85 Kenagy RD, Vergel S, Mattsson E, Bendeck M, Reidy MA, Clowes AW. The role of plasminogen, plasminogen activators, and matrix metalloproteinases in primate arterial smooth muscle cell migration. Arterioscler Thromb Vasc Biol 1996; 16: 1373-1382.
• 86 Aoyagi M, Yamamoto M, Azuma H, Nagashima G, Niimi Y, Tamaki M, Hirakawa K, Yamamoto K. Immunolocalization of matrix metalloproteinases in rabbit carotid arteries after balloon denudation. Histochem Cell Biol 1998; 109: 97-102.
• 87 Carmeliet P, Moons L, Ploplis V, Plow E, Collen D. Impaired arterial neointima formation in mice with disruption of the plasminogen gene. J Clin Invest 1997; 99: 200-208.
• 88 Carmeliet P, Moons L, Herbert J-M, Crawley J, Lupu F, Lijnen HR, Collen D. Urokinase-type but not tissue-type plasminogen activator mediates arterial neointima formation in mice. Circ Res 1997; 81: 829-839.
• 89 Lijnen HR, Lupu F, Moons L, Carmeliet P, Goulding D, Collen D. Temporal and topographic matrix metalloproteinase expression after vascular injury in mice. Thromb Haemost 1999; 8A: 799-807.
• 90 Lee E, Vaughan DE, Parikh SH, Grodzinsky AJ, Libby P, Lark MW, Lee RT. Regulation of matrix metalloproteinases and plasminogen activator inhibitor-1 synthesis by plasminogen in cultured human vascular smooth muscle cells. Circ Res 1996; 78: 44-49.
• 91 Okada A, Tomasetto C, Lutz Y, Bellocq JP, Rio MC, Basset P. Expression of matrix metalloproteinases during rat skin wound healing: evidence that membrane type-1 matrix metalloproteinase is a stromal activator of pro-gelatinase A. J Cell Biol 1997; 137: 67-77.
• 92 Shofuda K, Yasumitsu H, Nishihashi A, Miki K, Miyazaki K. Expression of three membrane-type matrix metalloproteinases (MT-MMPs) in rat vascular smooth muscle cells and characterization of MT3-MMPs with and without transmembrane domain. J Biol Chem 1997; 272: 9749-9754.
• 93 Webb KE, Henney AM, Anglin S, Humphries SE, McEwan JR. Expression of matrix metalloproteinases and their inhibitor TIMP-1 in the rat carotid artery after balloon injury. Arterioscler Thromb Vasc Biol 1997; 17: 1837-1844.
• 94 Lijnen HR, Van Hoef B, Vanlinthout I, Verstreken M, Rio MC, Collen D. Accelerated neointima formation after vascular injury in mice with stromelysin-3 (MMP-11) gene inactivation. Arterioscler Thromb Vasc Biol.. In Press.
• 95 Masson R, Lefebvre O, Noël A, El Fahime M, Chenard MP, Wendling C, Kebers F, LeMeur M, Dierich A, Foidart JM, Basset P, Rio MC. In vivo evidence that the stromelysin-3 metalloproteinase contributes in a paracrine manner to epithelial cell malignancy. J Cell Biol 1998; 140: 1535-1541.
• 96 Mañez S, Mira E, del Mar Barbacid M, Ciprés A, Fernández-Resa P, Buesa JM, Mérida I, Aracil M, Márquez G, Martínez-A C. Identification of insulin-like growth factor-binding protein-1 as a potential physiological substrate for human stromelysin-3. J Biol Chem 1997; 272: 25706-25712.
• 97 Lijnen HR, Van Hoef B, Soloway P, Collen D. Tissue inhibitor type 1 of matrix metalloproteinases (TIMP-1) impairs arterial neointima formation after vascular injury in mice. Submitted for publication.
• 98 Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 1993; 362: 2844-2850.
• 99 Fuster V. Mechanisms leading to myocardial infarction: insights from studies of vascular biology. Circulation 1994; 90: 2126-2146.
• 100 Libby P. Molecular basis of the acute coronary syndromes. Circulation 1995; 91: 2844-2850.
• 101 Schneiderman J, Bordin GM, Engelberg I, Adar R, Seiffert D, Thinnes T, Bernstein EF, Dilley RB, Loskutoff DJ. Expression of fibrinolytic genes in atherosclerotic abdominal aortic aneurysm wall: a possible mechanism for aneurysm expansion. J Clin Invest 1995; 96: 639-645.
• 102 Lupu F, Heim DA, Bachmann F, Hurni M, Kakkar VV, Kruithof EK. Plasminogen activator expression in human atherosclerotic lesions. Arterioscler Thromb Vasc Biol 1995; 15: 1444-1455.
• 103 Plump AS, Smith JD, Hayek T, Aalto Setala K, Walsh A, Verstuyft JG, Rubin EM, Breslow JL. Severe hypercholesterolemia and atherosclerosis in apolipoprotein E-deficient mice created by homologous recombination in ES cells. Cell 1992; 71: 343-353.
• 104 Carmeliet P, Moons L, Lijnen HR, Baes M, Lemaître V, Tipping P, Drew A, Eeckhout Y, Shapiro S, Lupu F, Collen D. Urokinase-generated plasmin is a candidate activator of matrix metalloproteinases during atherosclerotic aneurysm formation. Nature Genet 1997; 17: 439-444.
• 105 Allaire E, Forough R, Clowes M, Starcher B, Clowes AW. Local overexpression of TIMP-1 prevents aortic aneurysm degeneration and rupture in a rat model. J Clin Invest 1998; 102: 1413-1420.