Published online before print June 5, 2008

This Article Full Text (Rapid PDF) All Versions of this Article: ajpath.2008.071046v1 173/1/278    most recent 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 Google Scholar Articles by Ho, B. Articles by Bendeck, M. P. PubMed PubMed Citation Articles by Ho, B. Articles by Bendeck, M. P.

Copyright © 2008 American Society for Investigative Pathology
American Journal of Pathology, doi:10.2353/ajpath.2008.071046

Accepted for publication April 9, 2008.

Article

Integrin-Linked Kinase in the Vascular Smooth Muscle Cell Response to Injury

Bernard Ho^*, Guangpei Hou^*, J. Geoffrey Pickering, Gregory Hannigan, B. Lowell Langille^*, and Michelle P. Bendeck^*@

From the Department of Laboratory Medicine and Pathobiology,* University of Toronto, Toronto, Ontario, Canada; the Robarts Research Institute, and the Department of Medicine, University of Western Ontario, London, Ontario, Canada; Monash Institute of Medical Research, Monash University, Melbourne, Australia; and Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada

^@ To whom correspondence should be addressed. E-mail: michelle.bendeck{at}utoronto.ca.

	Abstract

Integrin-mediated interactions between smooth muscle cells (SMCs) and the extracellular matrix regulate cell migration and proliferation during neointimal hyperplasia. Integrin-linked kinase (ILK) is a serine-threonine kinase and scaffolding molecule that acts downstream of integrin receptors to modulate cell adhesion; therefore, we examined ILK function in SMCs during wound repair. Silencing of ILK expression with siRNA in vitro decreased cell adhesion to fibronectin and accelerated both cell proliferation and wound closure in the cell monolayer; it also resulted in the rearrangement of focal adhesions and diminished central actin stress fibers. Akt and GSK3 are ILK substrates that are important in cell motility; however, ILK siRNA silencing did not attenuate injury-induced increases in Akt and GSK3 phosphorylation. Following balloon catheter injury of the rat carotid artery in vivo, a dramatic decrease in ILK levels coincided with both the proliferation and migration of SMCs, which leads to the formation of a thickened neointima. Immunostaining revealed decreased ILK levels in the media and deep layers of the neointima, but increased ILK levels in the subluminal layers of the intima. Taken together, these results suggest that ILK functions to maintain SMC quiescence in the normal artery. A decrease in ILK levels after injury may permit SMC migration, proliferation, and neointimal thickening, and its re-expression at the luminal surface may attenuate this process during later stages of the injury response.