Local delivery of VEGF adenovirus to the uterine artery increases vasorelaxation and uterine blood flow in the pregnant sheep

Autor: A L, David, B, Torondel, I, Zachary, V, Wigley, K, Abi-Nader, K A, Nader, V, Mehta, S M K, Buckley, T, Cook, M, Boyd, C H, Rodeck, J, Martin, D M, Peebles
Rok vydání: 2008
Předmět:
Zdroj: Gene Therapy. 15:1344-1350
ISSN: 1476-5462
0969-7128
DOI: 10.1038/gt.2008.102
Popis: 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
Databáze: OpenAIRE