This Article Full Text Full Text (PDF) Data Supplement Alert me when this article is cited 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 Kanda, S. Articles by Iguchi, A. Search for Related Content PubMed PubMed Citation Articles by Kanda, S. Articles by Iguchi, A. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Related Collections Mechanism of atherosclerosis/growth factors

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2000;20:998.)
© 2000 American Heart Association, Inc.

Vascular Biology

Matrix Metalloproteinase and vß3 Integrin–Dependent Vascular Smooth Muscle Cell Invasion Through a Type I Collagen Lattice

Shigeru Kanda; Masafumi Kuzuya; Miguel A. Ramos; Teruhiko Koike; Kohichiro Yoshino; Shoji Ikeda; Akihisa Iguchi

From the Department of Geriatrics (S.K., M.K., M.A.R., T.K., A.I.), Nagoya University Graduate School of Medicine, Nagoya; and R&D Laboratories (K.Y., S.I.), Nippon Organon, Osaka, Japan.

Correspondence to Shigeru Kanda, MD, Department of Geriatrics, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan. E-mail kanda3{at}spice.or.jp

Abstract—Smooth muscle cell (SMC) migration from the tunica media to the intima is a key event in the development of atherosclerotic lesions and in restenosis after angioplasty. SMCs require not only migratory but also degradative abilities that enable them to migrate through extracellular matrix proteins, which surround and embed these cells. We used a collagen type I lattice as a coating on top of a porous filter as a matrix barrier in a chamber to test the invasive behavior of SMCs in response to a chemoattractant (invasion assay) and compared that behavior with simple SMC migration through collagen type I–coated filters (migration assay). Inhibitors of matrix metalloproteinase, KB-R8301, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), TIMP-2, and peptide 74, attenuated platelet-derived growth factor-BB (PDGF-BB)–directed SMC invasion across the collagen lattice, whereas no effect was seen with these inhibitors on simple SMC migration through collagen-coated filters. RGD peptide inhibited SMC invasion but did not affect SMC migration. Anti-vß3 integrin antibody attenuated PDGF-BB–directed SMC invasion, whereas other antibodies against RGD-recognizing integrins, namely vß5 and 5, had no effect. None of these antibodies had any effect on simple SMC migration. RGD peptide and anti-vß3 antibody inhibited the attachment and spreading of SMCs on denatured collagen but not on native collagen. These findings indicate that there is a difference in the mechanisms between simple SMC migration across a collagen-coated filter and SMC invasion through a fibrillar collagen barrier. A proteolytic process is required for SMC invasion, and the degradation of matrix proteins alters the relationship between matrix protein molecules and SMC surface integrins.

Key Words: smooth muscle cells • integrins • collagen • matrix metalloproteinases • cell migration

This article has been cited by other articles:

				K. W. Lee, N. J. Kang, M.-H. Oak, M. K. Hwang, J. H. Kim, V. B. Schini-Kerth, and H. J. Lee Cocoa procyanidins inhibit expression and activation of MMP-2 in vascular smooth muscle cells by direct inhibition of MEK and MT1-MMP activities Cardiovasc Res, July 1, 2008; 79(1): 34 - 41. [Abstract] [Full Text] [PDF]

				R. Khan, A. Agrotis, and A. Bobik Understanding the role of transforming growth factor-{beta}1 in intimal thickening after vascular injury Cardiovasc Res, May 1, 2007; 74(2): 223 - 234. [Abstract] [Full Text] [PDF]

				D. Vigetti, P. Moretto, M. Viola, A. Genasetti, M. Rizzi, E. Karousou, F. Pallotti, G. De Luca, and A. Passi Matrix metalloproteinase 2 and tissue inhibitors of metalloproteinases regulate human aortic smooth muscle cell migration during in vitro aging FASEB J, June 1, 2006; 20(8): 1118 - 1130. [Abstract] [Full Text] [PDF]

				M. Kuzuya, K. Nakamura, T. Sasaki, X. Wu Cheng, S. Itohara, and A. Iguchi Effect of MMP-2 Deficiency on Atherosclerotic Lesion Formation in ApoE-Deficient Mice Arterioscler. Thromb. Vasc. Biol., May 1, 2006; 26(5): 1120 - 1125. [Abstract] [Full Text] [PDF]

				X. W. Cheng, M. Kuzuya, K. Nakamura, Q. Di, Z. Liu, T. Sasaki, S. Kanda, H. Jin, G.-P. Shi, T. Murohara, et al. Localization of Cysteine Protease, Cathepsin S, to the Surface of Vascular Smooth Muscle Cells by Association with Integrin {alpha}{nu}{beta}3 Am. J. Pathol., February 1, 2006; 168(2): 685 - 694. [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]

				X. W. Cheng, M. Kuzuya, K. Nakamura, Z. Liu, Q. Di, J. Hasegawa, M. Iwata, T. Murohara, M. Yokota, and A. Iguchi Mechanisms of the Inhibitory Effect of Epigallocatechin-3-Gallate on Cultured Human Vascular Smooth Muscle Cell Invasion Arterioscler. Thromb. Vasc. Biol., September 1, 2005; 25(9): 1864 - 1870. [Abstract] [Full Text] [PDF]

				X. W. Cheng, M. Kuzuya, T. Sasaki, S. Kanda, N. Tamaya-Mori, T. Koike, K. Maeda, E. Nishitani, and A. Iguchi Green tea catechins inhibit neointimal hyperplasia in a rat carotid arterial injury model by TIMP-2 overexpression Cardiovasc Res, June 1, 2004; 62(3): 594 - 602. [Abstract] [Full Text] [PDF]

				M. S. Aguzzi, C. Giampietri, F. De Marchis, F. Padula, R. Gaeta, G. Ragone, M. C. Capogrossi, and A. Facchiano RGDS peptide induces caspase 8 and caspase 9 activation in human endothelial cells Blood, June 1, 2004; 103(11): 4180 - 4187. [Abstract] [Full Text] [PDF]

				X. W. Cheng, M. Kuzuya, T. Sasaki, K. Arakawa, S. Kanda, D. Sumi, T. Koike, K. Maeda, N. Tamaya-Mori, G.-P. Shi, et al. Increased Expression of Elastolytic Cysteine Proteases, Cathepsins S and K, in the Neointima of Balloon-Injured Rat Carotid Arteries Am. J. Pathol., January 1, 2004; 164(1): 243 - 251. [Abstract] [Full Text] [PDF]

				M. Kuzuya, S. Kanda, T. Sasaki, N. Tamaya-Mori, X. W. Cheng, T. Itoh, S. Itohara, and A. Iguchi Deficiency of Gelatinase A Suppresses Smooth Muscle Cell Invasion and Development of Experimental Intimal Hyperplasia Circulation, September 16, 2003; 108(11): 1375 - 1381. [Abstract] [Full Text] [PDF]

				J.-M. Li, L. M. Fan, A. Shah, and G. Brooks Targeting {alpha}v{beta}3 and {alpha}5{beta}1 for gene delivery to proliferating VSMCs: synergistic effect of TGF-{beta}1 Am J Physiol Heart Circ Physiol, August 7, 2003; 285(3): H1123 - H1131. [Abstract] [Full Text] [PDF]

				G.-P. Shi, G.K. Sukhova, M. Kuzuya, Q. Ye, J. Du, Y. Zhang, J.-H. Pan, M.L. Lu, X.W. Cheng, A. Iguchi, et al. Deficiency of the Cysteine Protease Cathepsin S Impairs Microvessel Growth Circ. Res., March 21, 2003; 92(5): 493 - 500. [Abstract] [Full Text] [PDF]

				J. A. Nadal, G. M. Scicli, L. A. Carbini, and A. G. Scicli Angiotensin II stimulates migration of retinal microvascular pericytes: involvement of TGF-beta and PDGF-BB Am J Physiol Heart Circ Physiol, February 1, 2002; 282(2): H739 - H748. [Abstract] [Full Text] [PDF]

				Y. Zhu, H. Bujo, H. Yamazaki, S. Hirayama, T. Kanaki, K. Takahashi, M. Shibasaki, W. J. Schneider, and Y. Saito Enhanced Expression of the LDL Receptor Family Member LR11 Increases Migration of Smooth Muscle Cells In Vitro Circulation, April 16, 2002; 105(15): 1830 - 1836. [Abstract] [Full Text] [PDF]