Gene therapy, 2008-10, Vol.15 (19), p.1344-1350
2008
Details
- Autor(en) / Beteiligte
- Titel
- Local delivery of VEGF adenovirus to the uterine artery increases vasorelaxation and uterine blood flow in the pregnant sheep
- Ist Teil von
- Gene therapy, 2008-10, Vol.15 (19), p.1344-1350
- Ort / Verlag
- Basingstoke: Nature Publishing Group
- Erscheinungsjahr
- 2008
- Link zum Volltext
- Quelle
- Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0969-7128eISSN: 1476-5462DOI: 10.1038/gt.2008.102Titel-ID: cdi_proquest_miscellaneous_69546387
- Format
- –
- Schlagworte
- Adenoviridae - genetics, Adenovirus, Adenoviruses, Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy, Animals, Applied cell therapy and gene therapy, Arteries, Biological and medical sciences, Biotechnology, Blood flow, Bradykinin, Care and treatment, Causes of, Contractility, Enzyme-Linked Immunosorbent Assay, Expression vectors, Female, Fetal Growth Retardation - physiopathology, Fetal Growth Retardation - therapy, Fetuses, Fundamental and applied biological sciences. Psychology, Gene Expression, Gene therapy, Genetic Therapy - methods, Genetic Vectors - administration & dosage, Genetic Vectors - genetics, Health aspects, Health. Pharmaceutical industry, Hypertension, Industrial applications and implications. Economical aspects, Injection, Injections, Intravenous, Medical sciences, Models, Animal, Obstetrics, Perfusion, Phenylephrine, Physiological aspects, Placental Circulation, Pre-eclampsia, Pregnancy, Pregnancy, Complications of, Prenatal development, Regional Blood Flow, Reporter gene, Reverse Transcriptase Polymerase Chain Reaction, Sheep, Transduction, Genetic - methods, Transfusions. Complications. Transfusion reactions. Cell and gene therapy, Ultrasonography, Uterus, Uterus - diagnostic imaging, Vascular endothelial growth factor, Vascular Endothelial Growth Factor A - analysis, Vascular Endothelial Growth Factor A - genetics, Vasodilation, Vasodilation - genetics, Veins & arteries, Viruses, β-Galactosidase