The in vivo and in vitro effects on neovascularization of VEGF gene transfer with a new pseudotyped rAAV1 vector / 中华心血管病杂志
Chinese Journal of Cardiology
; (12): 69-73, 2007.
Artigo
em Chinês
| WPRIM (Pacífico Ocidental)
| ID: wpr-304965
Biblioteca responsável:
WPRO
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the effects of vascular endothelial growth factor (VEGF) gene transfer with a new pseudotyped recombinant adeno-associated virus (rAAV) vector with AAV serotype 1 capsid protein (rAAV1) vector on neovascularization.</p><p><b>METHODS</b>PBS, rAAV1-GFP and rAAV1-VEGF vectors were added in C2C12 derived myotubes [10(5) vg (vector genomes) per cell]. Transfer efficiency was determined by fluorescent microscope and VEGF protein concentration in the culture media measured by ELISA. Ten days following ischemia in a hindlimb ischemic mouse model, PBS, 3 x 10(11)vg rAAV1-LacZ vectors and rAAV1-VEGF165 vectors were injected in ischemic thigh muscles. VEGF protein at ischemic thigh muscle was measured by ELISA at 1 month after vector infection. Capillaries and arterioles were observed by immunohistochemical analysis at 6 weeks after vector infection.</p><p><b>RESULTS</b>GFP expression was found in 60% - 80% myotubes at 120 hours after rAAV1-GFP infection. VEGF protein peaked at the 3rd day post rAAV1-VEGF infection with an average concentration of (567.7 +/- 16.8) pg/ml. Transfer efficacy in ischemic thigh muscle was 100% one month post rAAV1-LacZ infection. The average concentration of VEGF protein in ischemic skeletal muscles is (205.4 +/- 36.1) pg/mg total protein in rAAV1-VEGF165 treated mice. Extensive angiogenesis [(147.0 +/- 13.3)/mm(2)] and arteriogenesis [(17.0 +/- 1.2)/mm(2)] were observed in ischemic skeletal muscles at 6 weeks post rAAV1-VEGF165 injection.</p><p><b>CONCLUSION</b>Gene transfer with the new pseudotyped rAAV1-VEGF165 vector might be an effective therapeutic approach for ischemic cardiovascular diseases.</p>
Texto completo:
Disponível
Base de dados:
WPRIM (Pacífico Ocidental)
Assunto principal:
Terapêutica
/
Transdução Genética
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Terapia Genética
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Linhagem Celular
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Isquemia Miocárdica
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Dependovirus
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Neovascularização Fisiológica
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Proteínas do Capsídeo
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Fator A de Crescimento do Endotélio Vascular
/
Vetores Genéticos
Tipo de estudo:
Estudo prognóstico
Limite:
Animais
Idioma:
Chinês
Revista:
Chinese Journal of Cardiology
Ano de publicação:
2007
Tipo de documento:
Artigo