Abstract
Vascular hypertrophy may increase the blood pressure by its effect on vascular resistance. In this study, adenoviral gene transfer of IFN-β was analysed in a porcine model of balloon injury to determine whether a secreted growth inhibitory protein might affect the regrowth of vascular smooth muscle cells (VSMC) in vitro and in arteries. An adenoviral vector encoding IFN-β (ADV-IFN-β) was constructed by homologous recombination between sub360 genomic DNA, an ADV 5 derivative with a deletion in the E3 region and a porcine IFN-β expression plasmid, its antiproliferatire effect was analysed using cell proliferation assays, and used in a porcine model of balloon injury. After injury, arteries were immediately transfected with 7 x 10 9 plaques forming units of either ADV-INF-β or a control E1A deficient adenovirus that does not encode a recombinant protein, ADV-ΔE1. The intima/media (I/M) area ratio was determined by quantitative morphometry 21 days after artery injury and gene transfer. Expression of recombinant porcine IFN-β in VSMC reduced cell proliferation significantly in vitro, and supernatants derived from INF-β vector infected cells inhibited VSMC proliferation relative to controls. When introduced into porcine arteries after balloon injury, a reduction in I/M ratio of 30% was found. I/M ratio in the IFN-β transduced arteries was 0.54 ± 0.03 vs 0.69 ± 0.06 in ADV-ΔE1 transfected arteries and 0.702 ± 0.05 in the non-transfected arteries. Gene transfer of an adenoviral vector encoding IFN-β to VSMC and injured arteries reduced cell proliferation and vascular thickening. This approach is potentially applicable to vascular proliferative diseases.
Translated title of the contribution | Inhibition of vascular smooth muscle cell proliferation and intimal hyperplasia by gene transfer of interferon beta (INF-β) |
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Original language | French |
Pages (from-to) | 1121-1125 |
Number of pages | 5 |
Journal | Archives des Maladies du Coeur et des Vaisseaux |
Volume | 90 |
Issue number | 8 |
State | Published - 1997 |
Externally published | Yes |
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine