Local delivery of VEGF adenovirus to the uterine artery increases vasorelaxation and uterine blood flow in the pregnant sheep.
Gene Ther
; 15(19): 1344-50, 2008 Oct.
Article
em En
| MEDLINE
| ID: mdl-18563186
ABSTRACT
Impaired materno-placental perfusion causes two important obstetric complications, fetal growth restriction and preeclampsia. This study investigated whether adenoviral vector-mediated overexpression of vascular endothelial growth factor (VEGF) in the uterine arteries (UtAs) increases uterine artery blood flow (UBF). First-generation adenovirus vectors (5 x 10(11) particles) containing the VEGF gene (Ad.VEGF-A or -D) or the beta-galactosidase reporter gene (Ad.lacZ) were injected into the UtAs of pregnant sheep (n=6) at 88-102 days of gestation (term=145 days). UBF was measured using Doppler sonography before, and 4-7 days after injection. Mean UBF increased significantly from 233+/-156 (s.d.) ml min(-1) to 753+/-415 ml min(-1) following Ad.VEGF-A injection (P=0.005, n=5); Ad.lacZ infection had no significant effect. Organ bath experiments on uterine arterial sections 4-7 days after injection showed that, compared with Ad.lacZ vessels, Ad.VEGF-A-transduced vessels had a reduced contractile response to phenylephrine (E max 148+/-10.9 vs E max 228.2+/-27.5, P<0.05) but increased relaxation with bradykinin (pD2 (-log EC50) values 9.11+/-0.01 vs 8.65+/-0.11, P<0.05). Injection of Ad.VEGF-A into the UtAs increases UBF by enhancing vasodilatation. This may provide the basis for therapy in pregnancies complicated by uteroplacental insufficiency.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução Genética
/
Terapia Genética
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Adenoviridae
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Fator A de Crescimento do Endotélio Vascular
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Retardo do Crescimento Fetal
/
Vetores Genéticos
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Animals
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Pregnancy
Idioma:
En
Revista:
Gene Ther
Ano de publicação:
2008
Tipo de documento:
Article