(Circulation. 2001;103:3117.)
© 2001 American Heart Association, Inc.
Basic Science Reports |
Differential Expression of Matrix Metalloproteinases After Stent Implantation and Balloon Angioplasty in the Hypercholesterolemic Rabbit
From U460 INSERM (L.J.F., M.M, A.S., J.-F.D., E.D., C.B.-C., P.G.S., M.-P.J.) and Service d’Anatomo-Pathologie (D.H.), CHU Bichat, Paris, and Service de Pathologie Cellulaire/INSERM 99-24, CHU Grenoble (E.B.), France.
Correspondence to Laurent J. Feldman, MD, PhD, U460 INSERM, Faculté Xavier Bichat, 16, rue Henri Huchard, 75018 Paris, France. E-mail laurent.feldman{at}bch.ap-hop-paris.fr
Background—Intimal hyperplasia is the principal mechanism of in-stent restenosis. Matrix metalloproteinases (MMPs) play a key role in intimal growth after balloon angioplasty (BA). Little is known, however, about MMP expression after stent implantation (ST). We investigated whether MMP9 and MMP2 are differentially expressed after ST and BA.
Methods and
Results—Hypercholesterolemic
rabbits underwent ST and BA in the right and left iliac arteries,
respectively. The expression of MMPs and their inhibitors
(TIMPs) was studied at various time points in the injured arteries by
use of zymography, reverse transcription–polymerase chain reaction,
and immunohistochemistry. MMP2, but not MMP9, was constitutively
expressed in uninjured arteries. MMP9 expression was rapidly induced
after injury, whereas the increase in MMP2 expression was delayed. At
all time points, pro-MMP9 activity and MMP9 mRNA levels were 
2-fold
(ANOVA, P=0.002) and 3-fold
(P<0.0001) higher after ST
than after BA, respectively. Active MMP9 was detected only after ST.
Although the increases in MMP2 mRNA levels were of similar magnitudes
after ST and BA, pro-MMP2 activity was slightly higher 7 and 30 days
after ST, and MMP2 activity was 2-fold higher 7 to 60 days after ST
(P=0.002). No difference in
TIMP expression was observed between stented and balloon-injured
arteries. Cellular distributions of MMPs and TIMP1 were similar after
ST and BA. Early inflammatory cell recruitment and 30-day intimal
growth were more severe after ST.
Conclusions—Stent implantation results in more intense and sustained expression of MMP9 and activation of MMP2 than balloon angioplasty.
Key Words: metalloproteinases • stents • angioplasty • restenosis
This article has been cited by other articles:
 |
|
 |
|
  H. Hlawaty, A. San Juan, M.-P. Jacob, R. Vranckx, D. Letourneur, and L. J. Feldman Inhibition of MMP-2 gene expression with small interfering RNA in rabbit vascular smooth muscle cells Am J Physiol Heart Circ Physiol, December 1, 2007; 293(6): H3593 - H3601. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Uemura, M. Li, T. Tsutsumi, T. Yamazaki, T. Kawada, A. Kamiya, M. Inagaki, K. Sunagawa, and M. Sugimachi Efferent vagal nerve stimulation induces tissue inhibitor of metalloproteinase-1 in myocardial ischemia-reperfusion injury in rabbit Am J Physiol Heart Circ Physiol, October 1, 2007; 293(4): H2254 - H2261. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. A. Ali, N. J. Alp, H. Lupton, N. Arnold, T. Bannister, Y. Hu, S. Mussa, M. Wheatcroft, D. R. Greaves, J. Gunn, et al. Increased In-Stent Stenosis in ApoE Knockout Mice: Insights from a Novel Mouse Model of Balloon Angioplasty and Stenting Arterioscler. Thromb. Vasc. Biol., April 1, 2007; 27(4): 833 - 840. [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]
|
|
|
|
|
|
R. Sharony, G. Pintucci, P. C. Saunders, E. A. Grossi, F. G. Baumann, A. C. Galloway, and P. Mignatti Matrix metalloproteinase expression in vein grafts: role of inflammatory mediators and extracellular signal-regulated kinases-1 and -2 Am J Physiol Heart Circ Physiol, April 1, 2006; 290(4): H1651 - H1659. [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]
|
|
|
|
|
|
J. T. Peterson The importance of estimating the therapeutic index in the development of matrix metalloproteinase inhibitors Cardiovasc Res, February 15, 2006; 69(3): 677 - 687. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Hyafil, J.-P. Laissy, M. Mazighi, D. Tchetche, L. Louedec, H. Adle-Biassette, S. Chillon, D. Henin, M.-P. Jacob, D. Letourneur, et al. Ferumoxtran-10-Enhanced MRI of the Hypercholesterolemic Rabbit Aorta: Relationship Between Signal Loss and Macrophage Infiltration Arterioscler. Thromb. Vasc. Biol., January 1, 2006; 26(1): 176 - 181. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Krams, S. Verheye, L. C.A. van Damme, D. Tempel, B. M. Gourabi, E. Boersma, M. M. Kockx, M. W.M. Knaapen, C. Strijder, G. van Langenhove, et al. In vivo temperature heterogeneity is associated with plaque regions of increased MMP-9 activity Eur. Heart J., October 2, 2005; 26(20): 2200 - 2205. [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]
|
|
|
|
 |
|
 H. D. Danenberg, G. Golomb, A. Groothuis, J. Gao, H. Epstein, R. V. Swaminathan, P. Seifert, and E. R. Edelman Liposomal Alendronate Inhibits Systemic Innate Immunity and Reduces In-Stent Neointimal Hyperplasia in Rabbits Circulation, December 2, 2003; 108(22): 2798 - 2804. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Lu, K. Fukuda, K. Seki, Y. Nakamura, N. Kumagai, and T. Nishida Inhibition by Triptolide of IL-1-Induced Collagen Degradation by Corneal Fibroblasts Invest. Ophthalmol. Vis. Sci., December 1, 2003; 44(12): 5082 - 5088. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Fontaine, M.-P. Jacob, X. Houard, P. Rossignol, D. Plissonnier, E. Angles-Cano, and J.-B. Michel Involvement of the Mural Thrombus as a Site of Protease Release and Activation in Human Aortic Aneurysms Am. J. Pathol., November 1, 2002; 161(5): 1701 - 1710. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.-P. Jacob, M. Cazaubon, A. Scemama, D. Prie, F. Blanchet, M.-C. Guillin, and J.-B. Michel Plasma Matrix Metalloproteinase-9 as a Marker of Blood Stasis in Varicose Veins Circulation, July 30, 2002; 106(5): 535 - 538. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Li, W. J. Cantor, N. Nili, R. Robinson, L. Fenkell, Y. L. e Tran, H. A. Whittingham, W. Tsui, A. N. Cheema, J. D. Sparkes, et al. Arterial repair after stenting and the effects of gm6001, a matrix metalloproteinase inhibitor J. Am. Coll. Cardiol., June 5, 2002; 39(11): 1852 - 1858. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Chase, M. Bond, M. F. Crook, and A. C. Newby Role of Nuclear Factor-{kappa}B Activation in Metalloproteinase-1, -3, and -9 Secretion by Human Macrophages In Vitro and Rabbit Foam Cells Produced In Vivo Arterioscler. Thromb. Vasc. Biol., May 1, 2002; 22(5): 765 - 771. [Abstract] [Full Text] [PDF]
|
|