This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Pickering, J. G. Articles by Chan, B. M. C. Search for Related Content PubMed PubMed Citation Articles by Pickering, J. G. Articles by Chan, B. M. C.

(American Journal of Pathology. 2000;156:453-465.)
© 2000 American Society for Investigative Pathology

Regular Articles

5ß1 Integrin Expression and Luminal Edge Fibronectin Matrix Assembly by Smooth Muscle Cells after Arterial Injury

J. Geoffrey Pickering^*, Lawrence H. Chow^*, Shaohua Li^*, Kem A. Rogers^*, Edward F. Rocnik^§, Robert Zhong^¶ and Bosco M. C. Chan^||

From the John P. Robarts Research Institute (Vascular Biology Group), London Health Science Centre, Departments of Medicine (Cardiology),^*
Biochemistry,
Medical Biophysics,
Anatomy and Cell Biology,^§
Surgery,^¶
and Microbiology and Immunology,||
University of Western Ontario, London, Ontario, Canada

Fibronectin is secreted from the cell as a soluble protein that must then polymerize to regulate cell function. To elucidate the process of fibronectin matrix assembly in vascular disease, we immunostained sections of balloon-injured rat carotid artery for the fibronectin-binding 5ß1 integrin. Whereas 5ß1 integrin was not evident in the normal carotid artery, its expression was induced after a vascular injury. By 14 days, the 5ß1 integrin was localized exclusively to the less differentiated smooth muscle cells (SMCs) at the luminal surface of the neointima. Platelet-derived growth factor-BB, dominant in neointimal formation, selectively increased the expression of the 5ß1 integrin by human SMCs in culture. To track the assembly of fibronectin fibers, fluorescence-labeled soluble fibronectin protomers were added to cultured SMCs and to fresh segments of normal and balloon-injured rat carotid arteries. Fibronectin fiber formation in cultured SMCs could be detected within 10 minutes, and was blocked by an RGD peptide, an anti-ß1 integrin antibody, and an anti-5ß1 integrin antibody, but not by an anti-ß3 integrin antibody. En face confocal microscopy of arterial segments revealed that soluble fibronectin had polymerized on the 5ß1 integrin-expressing SMCs of the luminal surface of the injured arterial neointima, but not on the 5ß1 integrin-negative neointimal SMCs below this or on the endothelial cells of uninjured arteries. Furthermore, in situ fibronectin assembly by the neointimal SMCs was inhibited by an RGD peptide and by an anti-ß1 integrin antibody. These studies indicate that a subpopulation of SMCs in the repairing artery wall orchestrates integrin-mediated fibronectin assembly.

This article has been cited by other articles:

				M. J. Frontini, C. O'Neil, C. Sawyez, B. M.C. Chan, M. W. Huff, and J. G. Pickering Lipid Incorporation Inhibits Src-Dependent Assembly of Fibronectin and Type I Collagen by Vascular Smooth Muscle Cells Circ. Res., April 10, 2009; 104(7): 832 - 841. [Abstract] [Full Text] [PDF]

				B. Ho, G. Hou, J. G. Pickering, G. Hannigan, B. L. Langille, and M. P. Bendeck Integrin-Linked Kinase in the Vascular Smooth Muscle Cell Response to Injury Am. J. Pathol., July 1, 2008; 173(1): 278 - 288. [Abstract] [Full Text] [PDF]

				E. J. Ryer, R. P. Hom, K. Sakakibara, K. I. Nakayama, K. Nakayama, P. L. Faries, B. Liu, and K. C. Kent PKC{delta} Is Necessary for Smad3 Expression and Transforming Growth Factor {beta}-Induced Fibronectin Synthesis in Vascular Smooth Muscle Cells Arterioscler. Thromb. Vasc. Biol., April 1, 2006; 26(4): 780 - 786. [Abstract] [Full Text] [PDF]

				P. Brassard, F. Amiri, G. Thibault, and E. L. Schiffrin Role of Angiotensin Type-1 and Angiotensin Type-2 Receptors in the Expression of Vascular Integrins in Angiotensin II-Infused Rats Hypertension, January 1, 2006; 47(1): 122 - 127. [Abstract] [Full Text] [PDF]

				E. Fera, C. O'Neil, W. Lee, S. Li, and J. G. Pickering Fibroblast Growth Factor-2 and Remodeled Type I Collagen Control Membrane Protrusion in Human Vascular Smooth Muscle Cells: BIPHASIC ACTIVATION OF Rac1 J. Biol. Chem., August 20, 2004; 279(34): 35573 - 35582. [Abstract] [Full Text] [PDF]

				S. Li, C. Van Den Diepstraten, S. J. D'Souza, B. M. C. Chan, and J. G. Pickering Vascular Smooth Muscle Cells Orchestrate the Assembly of Type I Collagen via {alpha}2{beta}1 Integrin, RhoA, and Fibronectin Polymerization Am. J. Pathol., September 1, 2003; 163(3): 1045 - 1056. [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]

				M. Jones, P. J.B. Sabatini, F. S.H. Lee, M. P. Bendeck, and B. L. Langille N-Cadherin Upregulation and Function in Response of Smooth Muscle Cells to Arterial Injury Arterioscler. Thromb. Vasc. Biol., December 1, 2002; 22(12): 1972 - 1977. [Abstract] [Full Text] [PDF]

				D. Simper, P. G. Stalboerger, C. J. Panetta, S. Wang, and N. M. Caplice Smooth Muscle Progenitor Cells in Human Blood Circulation, September 3, 2002; 106(10): 1199 - 1204. [Abstract] [Full Text] [PDF]

				H. Ju, S. Nerurkar, C. F. Sauermelch, A. R. Olzinski, R. Mirabile, D. Zimmerman, J. C. Lee, J. Adams, J. Sisko, M. Berova, et al. Sustained Activation of p38 Mitogen-Activated Protein Kinase Contributes to the Vascular Response to Injury J. Pharmacol. Exp. Ther., April 1, 2002; 301(1): 15 - 20. [Abstract] [Full Text] [PDF]

				A. C. Newby Vitronectin is implicated as the matrix takes control of neointima formation Cardiovasc Res, March 1, 2002; 53(4): 779 - 781. [Full Text] [PDF]

				E. P. Moiseeva Adhesion receptors of vascular smooth muscle cells and their functions Cardiovasc Res, December 1, 2001; 52(3): 372 - 386. [Abstract] [Full Text] [PDF]

				K. L. Davenpeck, C. Marcinkiewicz, D. Wang, R. Niculescu, Y. Shi, J. L. Martin, and A. Zalewski Regional Differences in Integrin Expression : Role of {{alpha}}5{beta}1 in Regulating Smooth Muscle Cell Functions Circ. Res., February 16, 2001; 88(3): 352 - 358. [Abstract] [Full Text] [PDF]

				E. Rocnik, L. Saward, and J. G. Pickering HSP47 Expression by Smooth Muscle Cells Is Increased During Arterial Development and Lesion Formation and Is Inhibited by Fibrillar Collagen Arterioscler. Thromb. Vasc. Biol., January 1, 2001; 21(1): 40 - 46. [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]

				S. Li, Y.-S. Fan, L. H. Chow, C. Van Den Diepstraten, E. van der Veer, S. M. Sims, and J. G. Pickering Innate Diversity of Adult Human Arterial Smooth Muscle Cells: Cloning of Distinct Subtypes From the Internal Thoracic Artery Circ. Res., September 14, 2001; 89(6): 517 - 525. [Abstract] [Full Text] [PDF]