Send to

Choose Destination
Gene Ther. 2012 Sep;19(9):925-35. doi: 10.1038/gt.2011.158. Epub 2011 Oct 20.

Long-term increase in uterine blood flow is achieved by local overexpression of VEGF-A(165) in the uterine arteries of pregnant sheep.

Author information

Institute for Women's Health, University College London, London, UK.


Increasing uterine artery blood flow (UABF) may benefit fetal growth restriction where impaired uteroplacental perfusion prevails. Based on previous short-term results, we examined the long-term effects of adenovirus vector-mediated overexpression of vascular endothelial growth factor-A(165) (VEGF-A(165)) in the uterine artery (UtA). Transit-time flow probes were implanted around both UtAs of mid-gestation pregnant sheep (n=11) to measure UABF. A carotid artery catheter was inserted to measure maternal or fetal hemodynamics. Baseline UABF was measured over 3 days, before injection of adenovirus vector (5 × 10(11) particles) encoding the VEGF-A(165) gene (Ad.VEGF-A(165)) into one UtA and a reporter β-galactosidase gene (Ad.LacZ) contralaterally. UABF was then measured daily until term. At 4 weeks post injection, the increase in UABF was significantly higher in Ad.VEGF-A(165) compared with Ad.LacZ-transduced UtAs (36.53% vs 20.08%, P=0.02). There was no significant effect on maternal and fetal blood pressure. Organ bath studies showed significantly lesser vasoconstriction (E(max) 154.1 vs 184.7, P<0.001), whereas immunohistochemistry demonstrated a significantly increased number of adventitial blood vessels (140 vs 91, n=26, P<0.05) following Ad.VEGF-A(165) transduction. Local overexpression of VEGF-A(165) in the UtAs of pregnant mid-gestation sheep leads to a sustained long-term increase in UABF, which may be explained by neovascularization and altered vascular reactivity.

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center