Expression Patterns of Integrins on Quiescent and Invasive Smooth Muscle Cells and Impact on Cell Locomotion

• Published in: Journal of molecular and cellular cardiology Vol. 34; no. 12; pp. 1633 - 1644
• Main Authors: Blindt, Rüdiger, Krott, Nicole, Hanrath, Peter, vom Dahl, Jürgen, van Eys, Guillaume, Bosserhoff, Anja-Katrin
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-12-2002
• Subjects: Antibodies, Monoclonal; Atherosclerosis, Restenosis, Extracellular matrix, Smooth muscle; Cell Division; Cell Movement; Cells, Cultured; Collagen - metabolism; Fibronectins - metabolism; Flow Cytometry - methods; Genes, MHC Class I; Genes, MHC Class II; Humans; Integrins - chemistry; Integrins - classification; Integrins - metabolism; Mammary Arteries - anatomy & histology; Muscle, Smooth, Vascular - cytology; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - metabolism; Muscle, Smooth, Vascular - physiology; Atherosclerosis, Restenosis, Extracellular matrix, Smooth muscle
• ISSN: 0022-2828; 1095-8584
• DOI: 10.1006/jmcc.2002.2113

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.