Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
19
pubmed:dateCreated
2008-9-16
pubmed:abstractText
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.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1476-5462
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
15
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1344-50
pubmed:dateRevised
2008-12-30
pubmed:meshHeading
pubmed-meshheading:18563186-Adenoviridae, pubmed-meshheading:18563186-Animals, pubmed-meshheading:18563186-Arteries, pubmed-meshheading:18563186-Enzyme-Linked Immunosorbent Assay, pubmed-meshheading:18563186-Female, pubmed-meshheading:18563186-Fetal Growth Retardation, pubmed-meshheading:18563186-Gene Expression, pubmed-meshheading:18563186-Gene Therapy, pubmed-meshheading:18563186-Genetic Vectors, pubmed-meshheading:18563186-Injections, Intravenous, pubmed-meshheading:18563186-Models, Animal, pubmed-meshheading:18563186-Placental Circulation, pubmed-meshheading:18563186-Pregnancy, pubmed-meshheading:18563186-Regional Blood Flow, pubmed-meshheading:18563186-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:18563186-Sheep, pubmed-meshheading:18563186-Transduction, Genetic, pubmed-meshheading:18563186-Uterus, pubmed-meshheading:18563186-Vascular Endothelial Growth Factor A, pubmed-meshheading:18563186-Vasodilation
pubmed:year
2008
pubmed:articleTitle
Local delivery of VEGF adenovirus to the uterine artery increases vasorelaxation and uterine blood flow in the pregnant sheep.
pubmed:affiliation
Prenatal Gene Therapy Group, Institute for Women's Health, Royal Free and University College London Medical School, London, UK. a.david@ucl.ac.uk
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't