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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.
Artigo em Coreano | WPRIM | ID: wpr-100881
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.
Assuntos

Texto completo: DisponíveL Índice: WPRIM (Pacífico Ocidental) Assunto principal: Fenobarbital / Fosfotransferases / Timidina Quinase / DNA / Angiografia / Terapia Genética / Artérias Carótidas / Zidovudina / Ganciclovir / Morte Celular Limite: Animais Idioma: Coreano Revista: Korean Circulation Journal Ano de publicação: 1998 Tipo de documento: Artigo

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Texto completo: DisponíveL Índice: WPRIM (Pacífico Ocidental) Assunto principal: Fenobarbital / Fosfotransferases / Timidina Quinase / DNA / Angiografia / Terapia Genética / Artérias Carótidas / Zidovudina / Ganciclovir / Morte Celular Limite: Animais Idioma: Coreano Revista: Korean Circulation Journal Ano de publicação: 1998 Tipo de documento: Artigo