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Inhibition of vascular smooth muscle cell proliferation and migration in vitro and neointimal hyperplasia in vivo by adenoviral-mediated atrial natriuretic peptide delivery

Authors :
Larifla, Laurent
Deprez, Isabelle
Pham, Isabelle
Rideau, Dominique
Louzier, Vanessa
Adam, Micheline
Eloit, Marc
Foucan, Lydia
Adnot, Serge
Teiger, Emmanuel
Université des Antilles (UA)
Physiopathologie et Thérapeutiques Respiratoires
Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10
Génétique Moléculaire et Cellulaire (UGMC)
École nationale vétérinaire - Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)
ProdInra, Migration
École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)
Source :
The Journal of Gene Medicine, The Journal of Gene Medicine, Wiley, 2012, 14 (7), pp.459-467. ⟨10.1002/jgm.2639⟩
Publication Year :
2012
Publisher :
HAL CCSD, 2012.

Abstract

Chantier qualité GA; International audience; Background: Vascular smooth muscle cell (VSMC) proliferation and migration are important components of the remodeling process in atherosclerosis or following angioplasty. Atrial natriuretic peptide (ANP) inhibits the growth of VSMCs in vitro but this effect has not been proven in vivo. In the present study, we examined the effects of local overexpression of ANP following gene transfer on in vitro VSMC proliferation and migration and in vivo neointimal formation in a rat carotid artery model of vascular injury. Methods: ANP gene transfer was performed using a recombinant adenovirus containing the ANP cDNA controlled by the Rous sarcoma virus (RSV) long terminal repeat (Ad-RSV-ANP). A recombinant adenovirus expressing the RSV-controlled β-galactosidase gene (Ad-RSV-β-gal) was used as the control. Rat VSMC culture was used for in vitro studies. In the in vivo experiments, carotid arteries were analyzed after balloon injury and local infusion of the viral solution. Results: VSMCs transfected by Ad-RSV-ANP produced a significant amount of ANP detected by immunoreactive assay and accumulated about 6.5 times more cGMP than the viral control. VSMC proliferation stimulated with 10% fetal calf serum was reduced by 31% and migration by 25%. Fourteen days after injury, neointimal formation and the intima/media ratio were reduced by 25% and 28%, respectively, in the Ad-RSV-ANP-treated group compared to the control group. Conclusions: The present study demonstrates the efficacy of recombinant adenovirus Ad-RSV-ANP with respect to inhibiting rat VSMC proliferation and migration. Our findings also provide evidence that ANP is implicated in the modulation of vascular remodeling following endothelial injury.

Details

Language :
English
ISSN :
1099498X and 15212254
Database :
OpenAIRE
Journal :
The Journal of Gene Medicine, The Journal of Gene Medicine, Wiley, 2012, 14 (7), pp.459-467. ⟨10.1002/jgm.2639⟩
Accession number :
edsair.dedup.wf.001..d138b1194a05876b29ebaf6088cac780
Full Text :
https://doi.org/10.1002/jgm.2639⟩