© 1999 American Heart Association, Inc.
Integrative Physiology |
Matrix Metalloproteinase-9 Overexpression Enhances Vascular Smooth Muscle Cell Migration and Alters Remodeling in the Injured Rat Carotid Artery
From the Division of Vascular Surgery, (D.P.M., R.D.K., D.H., S.M.H., A.W.C.), Department of Surgery, and Department of Pathology (D.F.B.-P., R.A.S., S.C.), University of Washington, Seattle, Wash.
Correspondence to Alexander W. Clowes, MD, Division of Vascular Surgery, Department of Surgery, University of Washington School of Medicine, HSB BB442, Box 356410, 1959 NE Pacific St, Seattle, WA 98195-6410. E-mail clowes{at}u.washington.edu
Abstract—Matrix metalloproteinase-9 (MMP-9) has been implicated in the pathogenesis of atherosclerosis as well as intimal hyperplasia after vascular injury. We used Fischer rat smooth muscle cells (SMCs) overexpressing MMP-9 to determine the role of MMP-9 in migration and proliferation as well as in vessel remodeling after balloon denudation. Fischer rat SMCs were stably transfected with a cDNA for rat MMP-9 under the control of a tetracycline-regulatable promoter. In this system, MMP-9 was overexpressed in the absence, but not in the presence, of tetracycline. In vitro SMC migration was determined using a collagen invasion assay as well as a Boyden chamber assay. In vivo migration was determined by measuring the invasion into the medial and intimal layers of transduced SMCs seeded on the outside of the artery. Transduced SMCs were also seeded on the luminal surface, and the effect of local MMP-9 overexpression on vascular structure was measured morphometrically at intervals up to 28 days. MMP-9 overexpression enhanced SMC migration in both the collagen invasion assay and Boyden chamber in vitro, increased SMC migration into an arterial matrix in vivo, and altered vessel remodeling by increasing the vessel circumference, thinning the vessel wall and decreasing intimal matrix content. These results demonstrate that MMP-9 enhances vascular SMC migration in vitro and in vivo and alters postinjury vascular remodeling.
Key Words: matrix metalloproteinase-9 • migration • rat • smooth muscle cell • remodeling
This article has been cited by other articles:
 |
|
 |
|
  N. El-Bizri, C. Guignabert, L. Wang, A. Cheng, K. Stankunas, C.-P. Chang, Y. Mishina, and M. Rabinovitch SM22{alpha}-targeted deletion of bone morphogenetic protein receptor 1A in mice impairs cardiac and vascular development, and influences organogenesis Development, September 1, 2008; 135(17): 2981 - 2991. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Ogawa, J.-i. Suzuki, K. Hishikari, K. Takayama, H. Tanaka, and M. Isobe Clarithromycin Attenuates Acute and Chronic Rejection Via Matrix Metalloproteinase Suppression in Murine Cardiac Transplantation J. Am. Coll. Cardiol., May 20, 2008; 51(20): 1977 - 1985. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. R. S. Packard and P. Libby Inflammation in Atherosclerosis: From Vascular Biology to Biomarker Discovery and Risk Prediction Clin. Chem., January 1, 2008; 54(1): 24 - 38. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Toutouzas, A. Synetos, E. Stefanadi, S. Vaina, V. Markou, M. Vavuranakis, E. Tsiamis, D. Tousoulis, and C. Stefanadis Correlation Between Morphologic Characteristics and Local Temperature Differences in Culprit Lesions of Patients With Symptomatic Coronary Artery Disease J. Am. Coll. Cardiol., June 12, 2007; 49(23): 2264 - 2271. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. T. Gerthoffer Mechanisms of Vascular Smooth Muscle Cell Migration Circ. Res., March 16, 2007; 100(5): 607 - 621. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Zalba, A. Fortuno, J. Orbe, G. San Jose, M. U. Moreno, M. Belzunce, J. A. Rodriguez, O. Beloqui, J. A. Paramo, and J. Diez Phagocytic NADPH Oxidase-Dependent Superoxide Production Stimulates Matrix Metalloproteinase-9: Implications for Human Atherosclerosis Arterioscler. Thromb. Vasc. Biol., March 1, 2007; 27(3): 587 - 593. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. J. Mead, J. J. Maguire, R. E. Kuc, and A. P. Davenport Kisspeptins Are Novel Potent Vasoconstrictors in Humans, with a Discrete Localization of Their Receptor, G Protein-Coupled Receptor 54, to Atherosclerosis-Prone Vessels Endocrinology, January 1, 2007; 148(1): 140 - 147. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Abilleira, S. Bevan, and H. S Markus The role of genetic variants of matrix metalloproteinases in coronary and carotid atherosclerosis J. Med. Genet., December 1, 2006; 43(12): 897 - 901. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Qin, M. A. Corriere, L. M. Matrisian, and R. J. Guzman Matrix Metalloproteinase Inhibition Attenuates Aortic Calcification Arterioscler. Thromb. Vasc. Biol., July 1, 2006; 26(7): 1510 - 1516. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. T. Jones, I. P. Kay, J.W. S. Chu, G.T. Wilkins, L.V. Phillips, M. McCormick, A.M. van Rij, and M.J.A. Williams Elevated Plasma Active Matrix Metalloproteinase-9 Level Is Associated With Coronary Artery In-Stent Restenosis Arterioscler. Thromb. Vasc. Biol., July 1, 2006; 26(7): e121 - e125. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Fiotti, N. Altamura, M. Fisicaro, N. Carraro, L. Uxa, G. Grassi, L. Torelli, R. Gobbato, G. Guarnieri, B. T. Baxter, et al. MMP-9 Microsatellite Polymorphism and Susceptibility to Carotid Arteries Atherosclerosis Arterioscler. Thromb. Vasc. Biol., June 1, 2006; 26(6): 1330 - 1336. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. da Cunha, B. Martin-McNulty, J. Vincelette, L. Zhang, J. C. Rutledge, D. W. Wilson, R. Vergona, M. E. Sullivan, and Y.-X. Wang Interaction between mild hypercholesterolemia, HDL-cholesterol levels, and angiotensin II in intimal hyperplasia in mice J. Lipid Res., March 1, 2006; 47(3): 476 - 483. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. P.G. Sluijter, D. P.V. de Kleijn, and G. Pasterkamp Vascular remodeling and protease inhibition-bench to bedside Cardiovasc Res, February 15, 2006; 69(3): 595 - 603. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. C. Newby Matrix metalloproteinases regulate migration, proliferation, and death of vascular smooth muscle cells by degrading matrix and non-matrix substrates Cardiovasc Res, February 15, 2006; 69(3): 614 - 624. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Filippov, G. C. Koenig, T.-H. Chun, K. B. Hotary, I. Ota, T. H. Bugge, J. D. Roberts, W. P. Fay, H. Birkedal-Hansen, K. Holmbeck, et al. MT1-matrix metalloproteinase directs arterial wall invasion and neointima formation by vascular smooth muscle cells J. Exp. Med., September 6, 2005; 202(5): 663 - 671. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Honda, T. Kitano, F. Fukuya, Y. Sato, S. Iwama, T. Morie, and M. Notake A Novel {alpha}v{beta}3 Integrin Antagonist Suppresses Neointima Formation for More Than 4 Weeks After Balloon Injury in Rats Arterioscler. Thromb. Vasc. Biol., July 1, 2005; 25(7): 1376 - 1382. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Garcia-Touchard, T. D. Henry, G. Sangiorgi, L. G. Spagnoli, A. Mauriello, C. Conover, and R. S. Schwartz Extracellular Proteases in Atherosclerosis and Restenosis Arterioscler. Thromb. Vasc. Biol., June 1, 2005; 25(6): 1119 - 1127. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Burgstaller and M. Gimona Podosome-mediated matrix resorption and cell motility in vascular smooth muscle cells Am J Physiol Heart Circ Physiol, June 1, 2005; 288(6): H3001 - H3005. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. D. Defawe, R. D. Kenagy, C. Choi, S. Y.C. Wan, C. Deroanne, B. Nusgens, N. Sakalihasan, A. Colige, and A. W. Clowes MMP-9 regulates both positively and negatively collagen gel contraction: A nonproteolytic function of MMP-9 Cardiovasc Res, May 1, 2005; 66(2): 402 - 409. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. C. Newby Dual Role of Matrix Metalloproteinases (Matrixins) in Intimal Thickening and Atherosclerotic Plaque Rupture Physiol Rev, January 1, 2005; 85(1): 1 - 31. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Haug, C. Lenz, F. Diaz, and M. G. Bachem Oxidized Low-Density Lipoproteins Stimulate Extracellular Matrix Metalloproteinase Inducer (EMMPRIN) Release by Coronary Smooth Muscle Cells Arterioscler. Thromb. Vasc. Biol., October 1, 2004; 24(10): 1823 - 1829. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. M Ridker, N. J. Brown, D. E. Vaughan, D. G. Harrison, and J. L. Mehta Established and Emerging Plasma Biomarkers in the Prediction of First Atherothrombotic Events Circulation, June 29, 2004; 109(25_suppl_1): IV-6 - IV-19. [Full Text] [PDF]
|
|
|
|
|
|
C. L Burns-Kurtis, A. R Olzinski, S. Needle, J. H Fox, E. A Capper, F. M Kelly, M. S McQueney, and A. M Romanic Cathepsin S expression is up-regulated following balloon angioplasty in the hypercholesterolemic rabbit Cardiovasc Res, June 1, 2004; 62(3): 610 - 620. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Nakashima, M. Aoki, T. Miyake, T. Kawasaki, M. Iwai, N. Jo, M. Oishi, K. Kataoka, S. Ohgi, T. Ogihara, et al. Inhibition of Experimental Abdominal Aortic Aneurysm in the Rat by Use of Decoy Oligodeoxynucleotides Suppressing Activity of Nuclear Factor {kappa}B and ets Transcription Factors Circulation, January 6, 2004; 109(1): 132 - 138. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Johnson and Z. S. Galis Matrix Metalloproteinase-2 and -9 Differentially Regulate Smooth Muscle Cell Migration and Cell-Mediated Collagen Organization Arterioscler. Thromb. Vasc. Biol., January 1, 2004; 24(1): 54 - 60. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. E. Szmitko, C.-H. Wang, R. D. Weisel, G. A. Jeffries, T. J. Anderson, and S. Verma Biomarkers of Vascular Disease Linking Inflammation to Endothelial Activation: Part II Circulation, October 28, 2003; 108(17): 2041 - 2048. [Full Text] [PDF]
|
|
|
|
 |
|
 A. Castrillo, S. B. Joseph, C. Marathe, D. J. Mangelsdorf, and P. Tontonoz Liver X Receptor-dependent Repression of Matrix Metalloproteinase-9 Expression in Macrophages J. Biol. Chem., March 14, 2003; 278(12): 10443 - 10449. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Morishige, H. Shimokawa, Y. Matsumoto, Y. Eto, T. Uwatoku, K. Abe, K. Sueishi, and A. Takeshita Overexpression of matrix metalloproteinase-9 promotes intravascular thrombus formation in porcine coronary arteries in vivo Cardiovasc Res, February 1, 2003; 57(2): 572 - 585. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. S. Galis, C. Johnson, D. Godin, R. Magid, J. M. Shipley, R. M. Senior, and E. Ivan Targeted Disruption of the Matrix Metalloproteinase-9 Gene Impairs Smooth Muscle Cell Migration and Geometrical Arterial Remodeling Circ. Res., November 1, 2002; 91(9): 852 - 859. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Falkenberg, C. Tom, M. B. DeYoung, S. Wen, R. Linnemann, and D. A. Dichek Increased expression of urokinase during atherosclerotic lesion development causes arterial constriction and lumen loss, and accelerates lesion growth PNAS, August 6, 2002; 99(16): 10665 - 10670. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Urushihara, S. Kagami, T. Kuhara, T. Tamaki, and Y. Kuroda Glomerular distribution and gelatinolytic activity of matrix metalloproteinases in human glomerulonephritis Nephrol. Dial. Transplant., July 1, 2002; 17(7): 1189 - 1196. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Loftus and M. Thompson The role of matrix metalloproteinases in vascular disease Vascular Medicine, May 1, 2002; 7(2): 117 - 133. [Abstract] [PDF]
|
|
|
|
 |
|
 G. A. Limb, J. T. Daniels, R. Pleass, D. G. Charteris, P. J. Luthert, and P. T. Khaw Differential Expression of Matrix Metalloproteinases 2 and 9 by Glial Muller Cells : Response to Soluble and Extracellular Matrix-Bound Tumor Necrosis Factor-{alpha} Am. J. Pathol., May 1, 2002; 160(5): 1847 - 1855. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. S. Galis and J. J. Khatri Matrix Metalloproteinases in Vascular Remodeling and Atherogenesis: The Good, the Bad, and the Ugly Circ. Res., February 22, 2002; 90(3): 251 - 262. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. S. Cherr, S. J. Motew, J. A. Travis, J. Fingerle, L. Fisher, M. Brandl, J. K. Williams, and R. L. Geary Metalloproteinase Inhibition and the Response to Angioplasty and Stenting in Atherosclerotic Primates Arterioscler. Thromb. Vasc. Biol., January 1, 2002; 22(1): 161 - 166. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. V. Gurjar, J. Deleon, R. V. Sharma, and R. C. Bhalla Role of reactive oxygen species in IL-1beta -stimulated sustained ERK activation and MMP-9 induction Am J Physiol Heart Circ Physiol, December 1, 2001; 281(6): H2568 - H2574. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. A. Kingston, S. Sinha, A. David, M. G. Castro, P. R. Lowenstein, and A. M. Heagerty Adenovirus-Mediated Gene Transfer of a Secreted Transforming Growth Factor-{beta} Type II Receptor Inhibits Luminal Loss and Constrictive Remodeling After Coronary Angioplasty and Enhances Adventitial Collagen Deposition Circulation, November 20, 2001; 104(21): 2595 - 2601. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. R. Hauck, D. J. Sieg, D. A. Hsia, J. C. Loftus, W. A. Gaarde, B. P. Monia, and D. D. Schlaepfer Inhibition of Focal Adhesion Kinase Expression or Activity Disrupts Epidermal Growth Factor-stimulated Signaling Promoting the Migration of Invasive Human Carcinoma Cells Cancer Res., October 1, 2001; 61(19): 7079 - 7090. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. V. Gurjar, J. DeLeon, R. V. Sharma, and R. C. Bhalla Mechanism of inhibition of matrix metalloproteinase-9 induction by NO in vascular smooth muscle cells J Appl Physiol, September 1, 2001; 91(3): 1380 - 1386. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. J. Pollanen, P. J. Karhunen, J. Mikkelsson, P. Laippala, M. Perola, A. Penttila, K. M. Mattila, T. Koivula, and T. Lehtimaki Coronary Artery Complicated Lesion Area Is Related to Functional Polymorphism of Matrix Metalloproteinase 9 Gene: An Autopsy Study Arterioscler. Thromb. Vasc. Biol., September 1, 2001; 21(9): 1446 - 1450. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Hu, A. H. Baker, Y. Zou, A. C. Newby, and Q. Xu Local Gene Transfer of Tissue Inhibitor of Metalloproteinase-2 Influences Vein Graft Remodeling in a Mouse Model Arterioscler. Thromb. Vasc. Biol., August 1, 2001; 21(8): 1275 - 1280. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Hotary, E. Allen, A. Punturieri, I. Yana, and S. J. Weiss Regulation of Cell Invasion and Morphogenesis in a Three-dimensional Type I Collagen Matrix by Membrane-type Matrix Metalloproteinases 1, 2, and 3 J. Cell Biol., June 12, 2000; 149(6): 1309 - 1323. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|