Reduction of restenosis after angioplasty in an atheromatous rabbit model by suicide gene therapy.
Circulation
; 96(2): 408-11, 1997 Jul 15.
Article
en En
| MEDLINE
| ID: mdl-9244204
ABSTRACT
BACKGROUND:
Gene delivery of the thymidine kinase (tk) gene combined with ganciclovir (GCV) limits intimal hyperplasia after abrasion of normal arteries. However, the low efficiency of adenoviral-mediated gene transfer to atherosclerotic arteries has raised concerns about the applicability of this strategy to the prevention of restenosis. METHODS ANDRESULTS:
A replication-defective adenoviral vector expressing tk (Ad-RSVtk) demonstrated selective toxicity toward GCV-treated arterial smooth muscle cells, with oligonucleolytic cleavage suggesting apoptosis. In vivo, after demonstration of tk expression after Ad-RSVtk delivery, the combination of Ad-RSVtk followed by GCV was tested in a rabbit model of angioplasty of atheromatous iliac arteries. Angioplasty (8 atm, 20 minutes) was performed by use of a hydrogel balloon coated with Ad-RSVtk (4x10(9) plaque forming units). GCV was infused (25 mg.kg(-1) I.V. BID) from days 2 through 7 after angioplasty in 8 of 12 rabbits. Four weeks later, morphometric analysis demonstrated a reduced intima-to-media ratio in the group receiving combination therapy compared with Ad-RSVtk alone (3.0+/-1.2 versus 5.2+/-0.5, P<.018). GCV per se had no effect on intimal hyperplasia after arterial injury.CONCLUSIONS:
In vitro, Ad-RSVtk demonstrates selective toxicity toward GCV-treated arterial smooth muscle cells involving apoptosis. In vivo, GCV conditions reduction of neointimal formation after percutaneous delivery of Ad-RSVtk during angioplasty of atheromatous arteries.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Aorta
/
Arteriosclerosis
/
Timidina Quinasa
/
Terapia Genética
/
Angioplastia de Balón
Límite:
Animals
Idioma:
En
Revista:
Circulation
Año:
1997
Tipo del documento:
Article
País de afiliación:
Francia