Arteriosclerosis, Thrombosis, and Vascular Biology. 1996;16:28-33
© 1996 American Heart Association, Inc.
Articles |
Regulation of Vascular Smooth Muscle Cell Migration and Proliferation In Vitro and in Injured Rat Arteries by a Synthetic Matrix Metalloproteinase Inhibitor
From the Department of Surgery, University of Washington, Seattle.
Correspondence to Alexander W. Clowes, MD, Department of Surgery, RF-25, University of Washington, Seattle, WA 98195.
Abstract Smooth muscle cell (SMC) migration and proliferation and extracellular matrix remodeling are essential aspects of the arterial response to injury, vessel development, and atherogenesis. Matrix metalloproteinase (MMP) expression is associated with SMC proliferation and migration after arterial injury. To assess the role of MMPs in SMC proliferation and migration and intimal thickening, we measured the effect of the synthetic MMP inhibitor BB94 (Batimastat) on DNA synthesis and migration of SMCs in vitro as well as the formation of a neointima after balloon injury to the rat carotid artery. BB94 dose-dependently inhibited SMC migration induced by platelet-derived growth factor (PDGF)–BB through a filter coated with a thick basement membrane matrix (Matrigel) layer but did not show any inhibitory effect on SMC migration through a lightly coated filter. At concentrations up to 1 µmol/L, BB94 did not alter DNA synthesis induced by PDGF-AA or PDGF-BB. Treatment with 30 mg BB94·kg-1·d-1 IP for 7 or 14 days after balloon injury to the rat carotid artery decreased the total number of intimal SMC nuclei and suppressed intimal thickening. SMC proliferation (5-bromo-2'-deoxyuridine labeling) was decreased in the media at 2 days, whereas it was increased in the intima at 7 but not 14 days. These results suggest that BB94 inhibits intimal thickening after arterial injury by decreasing SMC migration and proliferation and support the conclusion that MMPs play a significant role in regulating intimal thickening in injured arteries.
Key Words: metalloproteinases • smooth muscle cells • rats • arterial injury • migration
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H. Wang and J. A. Keiser Vascular Endothelial Growth Factor Upregulates the Expression of Matrix Metalloproteinases in Vascular Smooth Muscle Cells : Role of flt-1 Circ. Res., October 19, 1998; 83(8): 832 - 840. [Abstract] [Full Text] [PDF]
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M. Janiszewski, C. A Pasqualucci, L. C Souza, F. Pileggi, P. L da Luz, and F. R M. Laurindo Oxidized thiols markedly amplify the vascular response to balloon injury in rabbits through a redox active metal-dependent pathway Cardiovasc Res, August 1, 1998; 39(2): 327 - 338. [Abstract] [Full Text] [PDF]
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H. S. Bassiouny, R. H. Song, X. F. Hong, A. Singh, H. Kocharyan, and S. Glagov Flow Regulation of 72-kD Collagenase IV (MMP-2) After Experimental Arterial Injury Circulation, July 14, 1998; 98(2): 157 - 163. [Abstract] [Full Text] [PDF]
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R. D. Kenagy, C. E. Hart, W. G. Stetler-Stevenson, and A. W. Clowes 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, November 18, 1997; 96(10): 3555 - 3560. [Abstract] [Full Text]
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S. J. George, J. L. Johnson, G. D. Angelini, and J. Y. Jeremy Short-term Exposure to Thapsigargin Inhibits Neointima Formation in Human Saphenous Vein Arterioscler Thromb Vasc Biol, November 1, 1997; 17(11): 2500 - 2506. [Abstract] [Full Text]
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J. G. Pickering, S. Uniyal, C. M. Ford, T. Chau, M. A. Laurin, L. H. Chow, C. G. Ellis, J. Fish, and B. M. C. Chan Fibroblast Growth Factor-2 Potentiates Vascular Smooth Muscle Cell Migration to Platelet-Derived Growth Factor : Upregulation of {alpha}2ß1 Integrin and Disassembly of Actin Filaments Circ. Res., May 19, 1997; 80(5): 627 - 637. [Abstract] [Full Text]
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A. Hultgardh-Nilsson, C. Lovdahl, K. Blomgren, Bengt Kallin, and J. Thyberg Expression of phenotype- and proliferation-related genes in rat aortic smooth muscle cells in primary culture Cardiovasc Res, May 1, 1997; 34(2): 418 - 430. [Abstract] [Full Text] [PDF]
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P. R. Moreno, V. H. Bernardi, J. Lopez-Cuellar, J. B. Newell, C. McMellon, H. K. Gold, I. F. Palacios, V. Fuster, and J. T. Fallon Macrophage Infiltration Predicts Restenosis After Coronary Intervention in Patients With Unstable Angina Circulation, December 15, 1996; 94(12): 3098 - 3102. [Abstract] [Full Text]
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R.D. Kenagy, S. Vergel, E. Mattsson, M. Bendeck, M.A. Reidy, and A.W. Clowes The Role of Plasminogen, Plasminogen Activators, and Matrix Metalloproteinases in Primate Arterial Smooth Muscle Cell Migration Arterioscler Thromb Vasc Biol, November 1, 1996; 16(11): 1373 - 1382. [Abstract] [Full Text]
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R. Forough, N. Koyama, D. Hasenstab, H. Lea, M. Clowes, S. T. Nikkari, and A. W. Clowes Overexpression of Tissue Inhibitor of Matrix Metalloproteinase-1 Inhibits Vascular Smooth Muscle Cell Functions In Vitro and In Vivo Circ. Res., October 1, 1996; 79(4): 812 - 820. [Abstract] [Full Text]
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S. Eguchi, P. J. Dempsey, G. D. Frank, E. D. Motley, and T. Inagami Activation of MAPKs by Angiotensin II in Vascular Smooth Muscle Cells. METALLOPROTEASE-DEPENDENT EGF RECEPTOR ACTIVATION IS REQUIRED FOR ACTIVATION OF ERK AND p38 MAPK BUT NOT FOR JNK J. Biol. Chem., March 9, 2001; 276(11): 7957 - 7962. [Abstract] [Full Text] [PDF]
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 C. Chassagne, C. Adamy, P. Ratajczak, B. Gingras, E. Teiger, E. Planus, P. Oliviero, L. Rappaport, J.-L. Samuel, and S. Meloche Angiotensin II AT2 receptor inhibits smooth muscle cell migration via fibronectin cell production and binding Am J Physiol Cell Physiol, April 1, 2002; 282(4): C654 - C664. [Abstract] [Full Text] [PDF]
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J.-S. Silvestre, Z. Mallat, R. Tamarat, M. Duriez, A. Tedgui, and B. I. Levy Regulation of Matrix Metalloproteinase Activity in Ischemic Tissue by Interleukin-10: Role in Ischemia-Induced Angiogenesis Circ. Res., August 3, 2001; 89(3): 259 - 264. [Abstract] [Full Text] [PDF]
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