Retrovirus-Mediated Herpes Simplex Virus Thymidine Kinase Gene Therapy for the Prevention of Stenosis in Rat Carotid Artery Injury Model
Korean Circulation Journal
; : 977-989, 1998.
Article
en Ko
| WPRIM
| ID: wpr-100881
Biblioteca responsable:
WPRO
ABSTRACT
BACKGROUND: Herpes simplex virus thymidine kinase (HSVtk) phosphorylates the prodrug ganciclovir to a nucleoside analog that inhibits DNA synthesis, causing cell death. Neighbouring nontransfected cells may be affected through a 'bystander effect', thereby amplifying the antiproliferative actions. This study was carried out to determine whether retrovirus-mediated HSVtk gene therapy could reduce intimal hyperplasia and prevent stenosis following balloon injury of the rat carotid artery. METHODS: A replication-defective recombinant retroviral vector containing HSVtk cDNA (LtkSN) was constructed. Cultured primary rat smooth muscle cells (SMCs) infected with this vector (SMC/LtkSN) were transplanted to the balloon injured rat right carotid artery. One week after transplantation, HSVtk gene therapy group was administered a 2-week treatment of ganciclovir (30 mg/kg/d). Three weeks after balloon injury and SMC/LtkSN transplantation, carotid arteriography was performed and carotid arteries were perfusion-fixed for histologic examination. RESULTS: Carotid arteriographic evaluation comparing with the uninjured left carotid artery showed that the mean luminal diameter of HSVtk gene therapy group (n=5, 85+/-3%) was significantly larger than that of balloon injury only group (n=5, 65+/-5%). The neointimal mass of HSVtk gene therapy group was less than that of balloon injury only group. SMC/LtkSN transplantation without ganciclovir treatment group (n=3) showed asymmetric intimal proliferation probably because of gravitational pooling of seeding. There were inflammatory cell infiltrations at the gravity dependent portion of HSVtk gene therapy group. CONCLUSION: Retrovirus-mediated HSVtk gene therapy following balloon injury of the rat carotid artery reduced neointimal expansion and arteriographic stenosis.
Palabras clave
Texto completo:
1
Base de datos:
WPRIM
Asunto principal:
Fenobarbital
/
Fosfotransferasas
/
Timidina Quinasa
/
ADN
/
Angiografía
/
Terapia Genética
/
Arterias Carótidas
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Zidovudina
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Ganciclovir
/
Muerte Celular
Límite:
Animals
Idioma:
Ko
Revista:
Korean Circulation Journal
Año:
1998
Tipo del documento:
Article