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Targeting αvβ3 and α5β1 for gene delivery to proliferating VSMCs: synergistic effect of TGF-β1

Li, J. M., Fan, L. M., Shah, A. and Brooks, G. (2003) Targeting αvβ3 and α5β1 for gene delivery to proliferating VSMCs: synergistic effect of TGF-β1. American Journal of Physiology-Heart and Circulatory Physiology, 285 (3). H1123-H1131. ISSN 0363-6135

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Official URL: http://ajpheart.physiology.org/content/285/3/H1123...

Abstract/Summary

TGF-beta1 levels increase after vascular injury and promote vascular smooth muscle cell (VSMC) proliferation. We define a nonviral gene delivery system that targets alphavbeta3 and alpha5beta1 integrins that are expressed on proliferating VSMCs and strongly induced by TGF-beta1. A 15-amino acid RGDNP-containing peptide from American Pit Viper venom was linked to a Lys(16) peptide as vector (molossin vector) and complexed with Lipofectamine or fusogenic peptide for delivery of luciferase or beta-galactosidase reporter genes to primary cultures of human, rabbit, and rat VSMCs. Preincubation of VSMCs with TGF-beta1 for 24 h, but not with PDGF-BB, interferon-gamma, TNF-alpha, nor PMA, increased alphavbeta3 and alpha5beta1 expressions on VSMCs and enhanced gene delivery of molossin vector. Thus beta-galactosidase activity increased from 35 +/- 5% (controls) to 75 +/- 5% after TGF-beta1 treatment, and luciferase activity increased fourfold over control values. Potential use of this system in vessel bypass surgery was examined in an ex vivo rat aortic organ culture model after endothelial damage. Molossin vector system delivered beta-galactosidase to VSMCs in the vessel wall that remained for up to 12 days posttransfection. The molossin vector system, when combined with TGF-beta1, enhances gene delivery to proliferating VSMCs and might have clinical applications for certain vasculoproliferative diseases.

Item Type:Article
Refereed:Yes
Divisions:Faculty of Life Sciences > School of Biological Sciences
Interdisciplinary centres and themes > Institute for Cardiovascular and Metabolic Research (ICMR)
ID Code:10806
Uncontrolled Keywords:integrin, peptide vector, molossin rector, SMOOTH-MUSCLE CELLS, INTEGRIN EXPRESSION, MEMBRANE INTEGRINS, NONVIRAL, VECTOR, DNA VECTOR, TGF-BETA, THERAPY, GROWTH, RECEPTOR, PEPTIDE
Additional Information:DOI 10.1152/ajpheart.00103.2003 not currently working Anglicised (Greek letters) version of Title: Targeting alpha v beta 3 and alpha 5 beta 1 for gene delivery to proliferating VSMCs: synergistic effect of TGF-beta 1
Publisher:American Physiological Society

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