This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 24/11/2123    most recent 01.ATV.0000141840.27300.fdv1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lessner, S. M. Articles by Galis, Z. S. Search for Related Content PubMed PubMed Citation Articles by Lessner, S. M. Articles by Galis, Z. S.

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:2123.)
© 2004 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Compensatory Vascular Remodeling During Atherosclerotic Lesion Growth Depends on Matrix Metalloproteinase-9 Activity

Susan M. Lessner; Deborah E. Martinson; Zorina S. Galis

From the Coulter Department of Biomedical Engineering (S.M.L., Z.S.G.) and the Department of Medicine (D.E.M.), Emory University School of Medicine, Atlanta, Ga.

Correspondence to Dr Susan M. Lessner, Emory University School of Medicine, Coulter Department of Biomedical Engineering, WMB 2001, 101 Woodruff Circle, Atlanta, GA 30322. E-mail slessne{at}emory.edu

Objective— The compensatory arterial remodeling associated with atherosclerotic plaques is thought to rely on the activity of matrix metalloproteinases (MMP). To assess the role of MMP-9, we analyzed the effect of MMP-9 genetic deficiency on the development and remodeling of experimental atherosclerotic lesions induced in the apolipoprotein E (apoE) knockout (–/–) mouse model.

Methods and Results— We analyzed remodeling parameters and cellular composition of experimental carotid artery atherosclerotic lesions in apoE–/– and apoE–/– MMP-9–/– double-knockout (DKO) mice at 0, 3, 7, and 14 days after induction by flow cessation. Morphometric image analysis of arterial tissue sections indicated that overall artery size, measured as area encompassed by the external elastic lamina, increased 3.1-fold in the apoE–/– mice but only 1.6-fold in the DKO mice (P<0.0001) by 14 days. At the same time, the net lesion area occupied by macrophages was similar. Statistical analysis indicated that the overall expansion of the artery was 2.5-fold less sensitive to macrophage content in DKO compared with apoE–/– mice. No compensatory increase in other gelatinolytic activities was detected in the DKO.

Conclusions— MMP-9 deficiency significantly impaired compensatory vessel enlargement during carotid artery lesion development in the apoE–/– mouse, without altering macrophage content of lesions.

MMP-9 deficiency impairs the compensatory outward remodeling during carotid lesion development in an apoE–/– mouse model of atherosclerosis without significantly altering neointimal macrophage accumulation. Arterial expansion becomes relatively insensitive to lesion macrophage content in the absence of MMP-9.

Key Words: matrix metalloproteinases • vascular remodeling • atherosclerosis • macrophages • transgenic mouse models

This article has been cited by other articles:

				B. Reel, G. Oktay, S. Ozkal, H. Islekel, E. Ozer, G. Ozsarlak-Sozer, Z. Cavdar, S. T. Akhisaroglu, and Z. Kerry MMP-2 and MMP-9 Alteration in Response to Collaring in Rabbits: The Effects of Endothelin Receptor Antagonism Journal of Cardiovascular Pharmacology and Therapeutics, December 1, 2009; 14(4): 292 - 301. [Abstract] [PDF]

				A. R. Lawrence and K. J. Gooch Transmural pressure and axial loading interactively regulate arterial remodeling ex vivo Am J Physiol Heart Circ Physiol, July 1, 2009; 297(1): H475 - H484. [Abstract] [Full Text] [PDF]

				M. Terashima, Y. Ohashi, H. Azumi, K. Otsui, H. Kaneda, K. Awano, S. Kobayashi, T. Honjo, T. Suzuki, K. Maeda, et al. Impact of NAD(P)H Oxidase-Derived Reactive Oxygen Species on Coronary Arterial Remodeling: A Comparative Intravascular Ultrasound and Histochemical Analysis of Atherosclerotic Lesions Circ Cardiovasc Interv, June 1, 2009; 2(3): 196 - 204. [Abstract] [Full Text] [PDF]

				S. Ohshima, A. Petrov, S. Fujimoto, J. Zhou, M. Azure, D. S. Edwards, T. Murohara, N. Narula, S. Tsimikas, and J. Narula Molecular Imaging of Matrix Metalloproteinase Expression in Atherosclerotic Plaques of Mice Deficient in Apolipoprotein E or Low-Density-Lipoprotein Receptor J. Nucl. Med., April 1, 2009; 50(4): 612 - 617. [Abstract] [Full Text] [PDF]

				E. Adiguzel, P. J Ahmad, C. Franco, and M. P Bendeck Collagens in the progression and complications of atherosclerosis Vascular Medicine, February 1, 2009; 14(1): 73 - 89. [Abstract] [PDF]

				P. C.Y. Tang, L. Qin, J. Zielonka, J. Zhou, C. Matte-Martone, S. Bergaya, N. van Rooijen, W. D. Shlomchik, W. Min, W. C. Sessa, et al. MyD88-dependent, superoxide-initiated inflammation is necessary for flow-mediated inward remodeling of conduit arteries J. Exp. Med., December 22, 2008; 205(13): 3159 - 3171. [Abstract] [Full Text] [PDF]

				J. Zhang, L. Nie, M. Razavian, M. Ahmed, L. W. Dobrucki, A. Asadi, D. S. Edwards, M. Azure, A. J. Sinusas, and M. M. Sadeghi Molecular Imaging of Activated Matrix Metalloproteinases in Vascular Remodeling Circulation, November 4, 2008; 118(19): 1953 - 1960. [Abstract] [Full Text] [PDF]

				S. M. Schwartz, Z. S. Galis, M. E. Rosenfeld, and E. Falk Plaque Rupture in Humans and Mice Arterioscler Thromb Vasc Biol, April 1, 2007; 27(4): 705 - 713. [Abstract] [Full Text] [PDF]

				P. Schoenhagen, E. M. Tuzcu, C. Apperson-Hansen, C. Wang, K. Wolski, S. Lin, I. Sipahi, S. J. Nicholls, W. A. Magyar, A. Loyd, et al. Determinants of Arterial Wall Remodeling During Lipid-Lowering Therapy: Serial Intravascular Ultrasound Observations From the Reversal of Atherosclerosis With Aggressive Lipid Lowering Therapy (REVERSAL) Trial Circulation, June 20, 2006; 113(24): 2826 - 2834. [Abstract] [Full Text] [PDF]

				J. L. Johnson, S. J. George, A. C. Newby, and C. L. Jackson Divergent effects of matrix metalloproteinases 3, 7, 9, and 12 on atherosclerotic plaque stability in mouse brachiocephalic arteries PNAS, October 25, 2005; 102(43): 15575 - 15580. [Abstract] [Full Text] [PDF]

				J. S. Ikonomidis, J. R. Barbour, Z. Amani, R. E. Stroud, A. R. Herron, D. M. McClister Jr, S. E. Camens, M. L. Lindsey, R. Mukherjee, and F. G. Spinale Effects of Deletion of the Matrix Metalloproteinase 9 Gene on Development of Murine Thoracic Aortic Aneurysms Circulation, August 30, 2005; 112(9_suppl): I-242 - I-248. [Abstract] [Full Text] [PDF]

				E. T. Choi, E. T. Collins, L. A. Marine, M. G. Uberti, H. Uchida, J. E. Leidenfrost, M. F. Khan, K. P. Boc, D. R. Abendschein, and W. C. Parks Matrix Metalloproteinase-9 Modulation by Resident Arterial Cells Is Responsible for Injury-Induced Accelerated Atherosclerotic Plaque Development in Apolipoprotein E-Deficient Mice Arterioscler Thromb Vasc Biol, May 1, 2005; 25(5): 1020 - 1025. [Abstract] [Full Text] [PDF]