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 |
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Rok vydání: | 2008 |
Předmět: |
Vascular Endothelial Growth Factor A
medicine.medical_specialty Genetic Vectors Gene Expression Hemodynamics Bradykinin Enzyme-Linked Immunosorbent Assay Vasodilation Adenoviridae Preeclampsia chemistry.chemical_compound Pregnancy Transduction Genetic medicine.artery Internal medicine Genetics medicine Animals Placental Circulation Uterine artery Molecular Biology Ultrasonography Fetal Growth Retardation Sheep Reverse Transcriptase Polymerase Chain Reaction business.industry Uterus Arteries Genetic Therapy medicine.disease Vascular endothelial growth factor Endocrinology medicine.anatomical_structure chemistry Regional Blood Flow Injections Intravenous Models Animal Circulatory system Molecular Medicine Female business Blood vessel |
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 |
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