Adenovirus-mediated delivery of Fas ligand inhibits intimal hyperplasia after balloon injury in immunologically primed animals

Adenoviral constructs have been used for studies of injury-induced vascular hyperplasia in immunologically naive laboratory animals, but their usefulness for intra-arterial gene therapy may be limited by the prevalence of preexisting immunity to adenovirus in the patient population. Here, we explore...

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Bibliographic Details
Published in:Circulation (New York, N.Y.) N.Y.), 1999-04, Vol.99 (14), p.1776-1779
Main Authors: ZHENGYU LUO, SATA, M, THAO NGUYEN, KAPLAN, J. M, AKITA, G. Y, WALSH, K
Format: Article
Language:English
Subjects:
Adenoviridae - genetics
Adenoviridae - immunology
Animals
Biological and medical sciences
Carotid Arteries - drug effects
Carotid Arteries - pathology
Carotid Artery Diseases - pathology
Carotid Artery Diseases - prevention & control
Catheterization
Diseases of the cardiovascular system
Fas Ligand Protein
Gene Transfer Techniques
Hyperplasia - prevention & control
Immunization
Male
Medical sciences
Membrane Glycoproteins - administration & dosage
Membrane Glycoproteins - genetics
Membrane Glycoproteins - pharmacology
Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects)
Rats
Rats, Sprague-Dawley
Tunica Intima - pathology
Vasculitis - prevention & control
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Summary:Adenoviral constructs have been used for studies of injury-induced vascular hyperplasia in immunologically naive laboratory animals, but their usefulness for intra-arterial gene therapy may be limited by the prevalence of preexisting immunity to adenovirus in the patient population. Here, we explored the efficacy of adenovirus-mediated transfer of Fas ligand, a cytotoxic gene with immunomodulatory properties, in inhibiting injury-induced vascular lesion formation in both naive and immunologically primed animals. Lesion formation was evaluated in balloon-injured carotid arteries of naive and adenovirus-immunized rats that were infected with adenoviral constructs expressing Fas ligand (Ad-FasL), the cyclin-dependent kinase inhibitor p21 (Ad-p21), or beta-galactosidase (Ad-betagal). In naive rats, Ad-FasL induced apoptosis in medial vascular smooth muscle cells and inhibited intimal hyperplasia by 60% relative to Ad-betagal-treated vessels (P
ISSN:0009-7322
1524-4539
DOI:10.1161/01.cir.99.14.1776