[en] Objective: Constrictive remodeling accounts for lumen loss in postangioplasty restenosis. Matrix metalloproteinase-9 (MMP-9) has been shown to prevent constrictive remodeling in vivo. To investigate potential mechanisms for this observation, we investigated the role of MMP-9 in smooth muscle cell (SMC)-mediated collagen gel contraction, an in vitro model of constrictive remodeling. Methods: Fischer rat SMCs were stably transfected with a construct-expressing rat-MMP-9 under the control of a tetracycline (Tet)-off promoter. SMCs were seeded in type 1 collagen gels (2.4 mg/ml) in the presence or not of tetracycline (1 mu g/ml), and gel contraction was defined as the percentage of retraction of the collagen gel. The depletion of MMP-9 was obtained by using siRNA targeting MMP-9 mRNA or a blocking antibody. Results: Gel contraction was significantly reduced at all times when MMP-9 was overexpressed (Tet-) as compared with the control condition (Tet+). However, MMP-9 depletion of control (Tet+) SMCS (using siRNA or antibody) also inhibited gel contraction. To resolve the apparent discrepancy and determine if MMP-9 exerts a dose-dependent biphasic effect on gel contraction, conditioned medium and purified rat-MMP-9 were prepared. Gel contraction was significantly increased by addition of 0.8 mg/ml of MMP-9, while high concentrations of MMP-9 (>= 100 mg/ml) inhibited contraction. The addition of BB94 and TIMP-1 did not alter the inhibitory or stimulatory effect of MMP-9. Conclusions: Our data Suggest that MMP-9, independent of its proteolytic function, has a biphasic effect on SMC-mediated collagen gel contraction. Understanding the different roles of MMP-9 Should allow the development of better therapeutic strategies for restenotic vascular disease. (c) 2004 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.
Disciplines :
Surgery Cardiovascular & respiratory systems
Author, co-author :
Defawe, Olivier D; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Laboratoire deBiologie des Tissus Conjonctifs
Kenagy, Richard D; University of Washington - Seattle,WA > Division of Vascular Surgery - Dpt of Surgery
Choi, Chun; University of Washington - Seattle,WA > Division of Vascular Surgery - Dpt of Surgery
Wan, Samuel Y C; University of Washington - Seattle,WA > Division of Vascular Surgery - Dpt of Surgery
Deroanne, Christophe ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Laboratoire des tissus conjonctifs
Nusgens, Betty ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Protéines et glycoprot. de matr.extracell. et membran.basal.
SakalihasanN, Natzi ; Centre Hospitalier Universitaire de Liège - CHU > Chirurgie cardio-vasculaire
Colige, Alain ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Laboratoire de BIologie des TissusConjonctifs
Clowes, Alexander W; University of Washington - Seattle,WA > Division of Vascular Surgery - Dpt of Surgery
Language :
English
Title :
MMP-9 regulates both positively and negatively collagen gel contraction - A nonproteolytic function of MMP-9
G. Pasterkamp, D.P. de Kleijn, and C. Borst Arterial remodeling in atherosclerosis, restenosis and after alteration of blood flow: potential mechanisms and clinical implications Cardiovasc. Res. 45 2000 843 852
G.H. Gibbons, and V.J. Dzau The emerging concept of vascular remodeling N. Engl. J. Med. 330 1994 1431 1438
D.P. Faxon, W. Coats, and J. Currier Remodeling of the coronary artery after vascular injury Prog. Cardiovasc. Dis. 40 1997 129 140
S.M. Schwartz, D. deBlois, and E.R. O'Brien The intima. Soil for atherosclerosis and restenosis Circ. Res. 77 1995 445 465
B.H. Strauss, R.J. Chisholm, F.W. Keeley, A.I. Gotlieb, R.A. Logan, and P.W. Armstrong Extracellular matrix remodeling after balloon angioplasty injury in a rabbit model of restenosis Circ. Res. 75 1994 650 658
D.W. Courtman, C.D. Franco, Q. Meng, and M.P. Bendeck Inward remodeling of the rabbit aorta is blocked by the matrix metalloproteinase inhibitor doxycycline J. Vasc. Res. 41 2004 157 165
Z.S. Galis, and J.J. Khatri Matrix metalloproteinases in vascular remodeling and atherogenesis: the good, the bad, and the ugly Circ. Res. 90 2002 251 262
D.P. Mason, R.D. Kenagy, D. Hasenstab, D.F. Bowen-Pope, R.A. Seifert, and S. Coats Matrix metalloproteinase-9 overexpression enhances vascular smooth muscle cell migration and alters remodeling in the injured rat carotid artery Circ. Res. 85 1999 1179 1185
S.M. Lessner, D.E. Martinson, and Z.S. Galis Compensatory vascular remodeling during atherosclerotic lesion growth depends on matrix metalloproteinase-9 activity Arterioscler. Thromb. Vasc. Biol. 24 2004 1 7
Z.S. Galis, C. Johnson, D. Godin, R. Magid, J.M. Shipley, and R.M. Senior Targeted disruption of the matrix metalloproteinase-9 gene impairs smooth muscle cell migration and geometrical arterial remodeling Circ. Res. 91 2002 852 859
F. Grinnell Fibroblasts, myofibroblasts, and wound contraction J. Cell Biol. 124 1994 401 404
R.L. Geary, S.T. Nikkari, W.D. Wagner, J.K. Williams, M.R. Adams, and R.H. Dean Wound healing: a paradigm for lumen narrowing after arterial reconstruction J. Vasc. Surg. 27 1998 96 106 [discussion 106-8]
C. Labarca, and K. Paigen A simple, rapid, and sensitive DNA assay procedure Anal. Biochem. 102 1980 344 352
R. Oltenfreiter, L. Staelens, A. Lejeune, F. Dumont, F. Frankenne, and J.M. Foidart New radioiodinated carboxylic and hydroxamic matrix metalloproteinase inhibitor tracers as potential tumor imaging agents Nucl. Med. Biol. 31 2004 459 468
C. Deroanne, V. Vouret-Craviari, B. Wang, and J. Pouyssegur EphrinA1 inactivates integrin-mediated vascular smooth muscle cell spreading via the Rac/PAK pathway J. Cell Sci. 116 2003 1367 1376
T. Morodomi, Y. Ogata, Y. Sasaguri, M. Morimatsu, and H. Nagase Purification and characterization of matrix metalloproteinase 9 from U937 monocytic leukaemia and HT1080 fibrosarcoma cells Biochem. J. 285 1992 603 611
N. Zempo, R.D. Kenagy, Y.P. Au, M. Bendeck, M.M. Clowes, and M.A. Reidy Matrix metalloproteinases of vascular wall cells are increased in balloon-injured rat carotid artery J. Vasc. Surg. 20 1994 209 217
C. Johnson, and Z.S. Galis Matrix metalloproteinase-2 and -9 differentially regulate smooth muscle cell migration and cell-mediated collagen organization [see comment] Arterioscler. Thromb. Vasc. Biol. 24 2004 54 60
B. Davies, P.D. Brown, N. East, M.J. Crimmin, and F.R. Balkwill A synthetic matrix metalloproteinase inhibitor decreases tumor burden and prolongs survival of mice bearing human ovarian carcinoma xenografts Cancer Res. 53 1993 2087 2091
H.R. Andersen, M. Maeng, M. Thorwest, and E. Falk Remodeling rather than neointimal formation explains luminal narrowing after deep vessel wall injury: insights from a porcine coronary (re)stenosis model [see comment] Circulation 93 1996 1716 1724
G.S. Mintz, J.J. Popma, A.D. Pichard, K.M. Kent, L.F. Satler, and C. Wong Arterial remodeling after coronary angioplasty: a serial intravascular ultrasound study Circulation 94 1996 35 43
M.J. Post, B.J. de Smet, Y. van der Helm, C. Borst, and R.E. Kuntz Arterial remodeling after balloon angioplasty or stenting in an atherosclerotic experimental model Circulation 96 1997 996 1003
T. Kimura, S. Kaburagi, T. Tamura, H. Yokoi, Y. Nakagawa, and N. Hamasaki Remodeling of human coronary arteries undergoing coronary angioplasty or atherectomy Circulation 96 1997 475 483
B.J. de Smet, D. de Kleijn, R. Hanemaaijer, J.H. Verheijen, L. Robertus, and Y.J. van Der Helm Metalloproteinase inhibition reduces constrictive arterial remodeling after balloon angioplasty: a study in the atherosclerotic Yucatan micropig Circulation 101 2000 2962 2967
M.J. Sierevogel, G. Pasterkamp, E. Velema, D.P.V. De Kleijn, B.J.G.L. De Smet, and P.P.T. De Jaegere Oral matrix metalloproteinase inhibition blocks constrictive arterial remodeling following ballon dilatation in the pig Circulation 103 2001 302 307
J.K. Karwowski, A. Markezich, J. Whitson, T.A. Abbruzzese, C.K. Zarins, and R.L. Dalman Dose-dependent limitation of arterial enlargement by the matrix metalloproteinase inhibitor RS-113,456 J. Surg. Res. 87 1999 122 129
D. Godin, E. Ivan, C. Johnson, R. Magid, and Z.S. Galis Remodeling of carotid artery is associated with increased expression of matrix metalloproteinases in mouse blood flow cessation model Circulation 102 2000 2861 2866
I.M. Loftus, S. Goodall, M. Crowther, L. Jones, P.R. Bell, and A.R. Naylor Increased MMP-9 activity in acute carotid plaques: therapeutic avenues to prevent stroke Ann. N.Y. Acad. Sci. 878 1999 551 554
P. Dandona, A. Aljada, P. Mohanty, H. Ghanim, A. Bandyopadhyay, and A. Chaudhuri Insulin suppresses plasma concentration of vascular endothelial growth factor and matrix metalloproteinase-9 Diabetes Care 26 2003 3310 3314
G. Pasterkamp, A.H. Schoneveld, D.J. Hijnen, D.P. de Kleijn, H. Teepen, and A.C. van der Wal Atherosclerotic arterial remodeling and the localization of macrophages and matrix metalloproteases 1, 2 and 9 in the human coronary artery Atherosclerosis 150 2000 245 253
M.D. Sternlicht, and Z. Werb How matrix metalloproteinases regulate cell behavior Annu. Rev. Cell Dev. Biol. 17 2001 463 516
P.C. Brooks, S. Stromblad, L.C. Sanders, T.L. von Schalscha, R.T. Aimes, and W.G. Stetler-Stevenson Localization of matrix metalloproteinase MMP-2 to the surface of invasive cells by interaction with integrin alpha v beta 3 Cell 85 1996 683 693
B. Levkau, R.D. Kenagy, A. Karsan, B. Weitkamp, A.W. Clowes, and R. Ross Activation of metalloproteinases and their association with integrins: an auxiliary apoptotic pathway in human endothelial cells Cell Death Differ. 9 2002 1360 1367
J.A. Travis, M.G. Hughes, J.M. Wong, W.D. Wagner, and R.L. Geary Hyaluronan enhances contraction of collagen by smooth muscle cells and adventitial fibroblasts: role of CD44 and implications for constrictive remodeling [see comment] Circ. Res. 88 2001 77 83
Q. Yu, and I. Stamenkovic Localization of matrix metalloproteinase 9 to the cell surface provides a mechanism for CD44-mediated tumor invasion Genes Dev. 13 1999 35 48
M.P. Skinner, E.W. Raines, and R. Ross Dynamic expression of alpha 1 beta 1 and alpha 2 beta 1 integrin receptors by human vascular smooth muscle cells. Alpha 2 beta 1 integrin is required for chemotaxis across type I collagen-coated membranes Am. J. Pathol. 145 1994 1070 1081
R.T. Lee, F. Berditchevski, G.C. Cheng, and M.E. Hemler Integrin-mediated collagen matrix reorganization by cultured human vascular smooth muscle cells Circ. Res. 76 1995 209 214
J.A. Schiro, B.M. Chan, W.T. Roswit, P.D. Kassner, A.P. Pentland, and M.E. Hemler Integrin alpha 2 beta 1 (VLA-2) mediates reorganization and contraction of collagen matrices by human cells Cell 67 1991 403 410
C.A. Partridge, P.G. Phillips, M.J. Niedbala, and J.J. Jeffrey Localization and activation of type IV collagenase/gelatinase at endothelial focal contacts Am. J. Physiol. 272 1997 L813 L822
T. Nassar, A. Haj-Yehia, S. Akkawi, A. Kuo, K. Bdeir, and A. Mazar Binding of urokinase to low density lipoprotein-related receptor (LRP) regulates vascular smooth muscle cell contraction J. Biol. Chem. 277 2002 40499 40504
T. Nassar, S. Akkawi, R. Bar-Shavit, A. Haj-Yehia, K. Bdeir, and A.B. Al-Mehdi Human alpha-defensin regulates smooth muscle cell contraction: a role for low-density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor Blood 100 2002 4026 4032
Y. Takayama, H. Takahashi, K. Mizumachi, and T. Takezawa Low density lipoprotein receptor-related protein (LRP) is required for lactoferrin-enhanced collagen gel contractile activity of human fibroblasts J. Biol. Chem. 278 2003 22112 22118
E. Hahn-Dantona, J.F. Ruiz, P. Bornstein, and D.K. Strickland The low density lipoprotein receptor-related protein modulates levels of matrix metalloproteinase 9 (MMP-9) by mediating its cellular catabolism J. Biol. Chem. 276 2001 15498 15503
R.P. Somerville, S.A. Oblander, and S.S. Apte Matrix metalloproteinases: old dogs with new tricks Genome Biol. 4 2003 216
