Abstract
R. Blindt, N. Krott, P. Hanrath, J. vom Dahl, G. van Eys and A.-K. Bosserhoff. Expression Patterns of Integrins on Quiescent and Invasive Smooth Muscle Cells and Impact on Cell Locomotion. Journal of Molecular and Cellular Cardiology (2002) 34, 1633–1644. Migration and invasion of human arterial smooth muscle cells (haSMCs) are essential steps during the development of atherosclerosis, restenosis, and transplant vasculopathy. The molecular mechanisms leading to these processes are only incompletely understood. Due to their contact to the surrounding extracellular matrix, integrins have been shown to be essentially involved in cell locomotion. Therefore, the function of integrins during this process was analyzed in an in vitro model which was based on the defined quiescent and invasive phenotypes of human haSMCs induced by cell culture conditions. Flow-cytometric analysis of integrin expression between both phenotypes showed a strong upregulation of alpha 5 beta 1 (13.1×) and a modest upregulation of alpha vs beta 3 (3.4×) and alpha IIb (3.0×) in invasive haSMCs in comparison to quiescent ones. Other integrins analyzed (alpha 2, alpha 3, alpha 4, beta 1) did not show differential regulation. Functional inhibition of alpha 5 beta 1 reduced cell migration (−29%±8), invasion (−49%±16), collagen contraction (−125%), and attachment to fibronectin. Although, there was a clear discrepancy between alpha 5 beta 1 and alpha vs beta 3 expression levels, inhibition of alpha vs beta 3 (−45%±9) reduced haSMC invasion equally. Interestingly, alpha vs beta 3 unlike alpha 5 beta 1 blockade caused a significant stimulation of collagen contraction (+52% vs 154%) with possible implications on vascular remodeling. In conclusion, alpha 5 beta 1 blockade or combined alpha 5 beta 1/alpha v beta 3 blockade by specific antibodies or selective RGD peptides together with local drug delivery strategies could be a promising strategy for the therapy of restenotic lesions or atheromatous plaques.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
