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

David, A L; Torondel, B; Zachary, I; Wigley, V; Nader, K A; Mehta, V; Buckley, S M K; Cook, T; Boyd, M; Rodeck, C H; Martin, J; Peebles, D M

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

Citation

David, A. L., Torondel, B., Zachary, I., Wigley, V., Nader, K. A., Mehta, V., Buckley, S. M. K., Cook, T., Boyd, M., Rodeck, C. H., Martin, J., & Peebles, D. M. Local delivery of VEGF adenovirus to the uterine artery increases vasorelaxation and uterine blood flow in the pregnant sheep. Gene Therapy, 15(19), 1344-1350. https://doi.org/10.1038/Gt.2008.102

• Journal Article Type: Article
• Deposit Date: Nov 11, 2014
• Journal: Gene Therapy
• Print ISSN: 0969-7128
• Electronic ISSN: 1476-5462
• Publisher: Springer Nature [academic journals on nature.com]
• Volume: 15
• Issue: 19
• Pages: 1344-1350
• DOI: https://doi.org/10.1038/Gt.2008.102
• Public URL: https://rvc-repository.worktribe.com/output/1429053
• Additional Information: Corporate Creators : Imperial College London, Royal Free