Expression patterns of integrins on quiescent and invasive smooth muscle cells and impact on cell locomotion
| Autor: | Peter Hanrath, Nicole Krott, Jürgen vom Dahl, Rüdiger Blindt, Anja-Katrin Bosserhoff, Guillaume J.J.M. van Eys |
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| Rok vydání: | 2002 |
| Předmět: |
Integrins
Alpha-v beta-3 Integrin Genes MHC Class II Alpha (ethology) Genes MHC Class I Muscle Smooth Vascular Extracellular matrix chemistry.chemical_compound Downregulation and upregulation Cell Movement Humans Mammary Arteries Molecular Biology Cells Cultured biology Antibodies Monoclonal Cell migration Flow Cytometry Cell biology Fibronectins Fibronectin chemistry Cell culture Immunology biology.protein Collagen Cardiology and Cardiovascular Medicine Cell Division |
| Zdroj: | Journal of molecular and cellular cardiology. 34(12) |
| ISSN: | 0022-2828 |
| Popis: | 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 (13.1x) and a modest upregulation of alpha vs beta 3 (3.4x) and alpha IIb (3.0x) 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. |
| Databáze: | OpenAIRE |
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