Le transfert du gene de l'interferon beta inhibe la proliferation des cellules musculaires lisses in vitro et dans un modele animal de lesion arterielle

Translated title of the contribution: Inhibition of vascular smooth muscle cell proliferation and intimal hyperplasia by gene transfer of interferon beta (INF-β)

D. Stephan, H. San, D. Gordon, G. J. Nabel, E. G. Nabel

Research output: Contribution to journalArticlepeer-review

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 contributionInhibition of vascular smooth muscle cell proliferation and intimal hyperplasia by gene transfer of interferon beta (INF-β)
Original languageFrench
Pages (from-to)1121-1125
Number of pages5
JournalArchives des Maladies du Coeur et des Vaisseaux
Volume90
Issue number8
StatePublished - 1997
Externally publishedYes

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'Inhibition of vascular smooth muscle cell proliferation and intimal hyperplasia by gene transfer of interferon beta (INF-β)'. Together they form a unique fingerprint.

Cite this