Inhibition of vascular smooth muscle cell proliferation and migration in vitro and neointimal hyperplasia in vivo by adenoviral-mediated atrial natriuretic peptide delivery
| Autor: | Serge Adnot, Marc Eloit, Laurent Larifla, Isabelle Deprez, Isabelle Pham, Vanessa Louzier, Micheline Adam, Lydia Foucan, Dominique Rideau, Emmanuel Teiger |
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| Rok vydání: | 2012 |
| Předmět: |
Neointimal hyperplasia
Rous sarcoma virus medicine.medical_specialty Vascular smooth muscle Intimal hyperplasia biology medicine.drug_class Chemistry viruses Transfection biology.organism_classification medicine.disease Endocrinology Atrial natriuretic peptide In vivo Internal medicine Drug Discovery cardiovascular system Genetics medicine Natriuretic peptide Molecular Medicine Molecular Biology hormones hormone substitutes and hormone antagonists Genetics (clinical) |
| Zdroj: | The Journal of Gene Medicine. 14:459-467 |
| ISSN: | 1099-498X |
| DOI: | 10.1002/jgm.2639 |
| Popis: | 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. Copyright © 2012 John Wiley & Sons, Ltd. |
| Databáze: | OpenAIRE |
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