Long-term increase in uterine blood flow is achieved by local overexpression of VEGF-A(165) in the uterine arteries of pregnant sheep.
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.
Institute for Women's Health, University College London, London, UK. v.mehta@ucl.ac.uk
V
V
Mehta
K N
KN
Abi-Nader
D M
DM
Peebles
E
E
Benjamin
V
V
Wigley
B
B
Torondel
E
E
Filippi
S W
SW
Shaw
M
M
Boyd
J
J
Martin
I
I
Zachary
A L
AL
David
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D062186:Arterial Pressure; D005260:Female; D005317:Fetal Growth Retardation / Q000503:physiopathology; D005822:Genetic Vectors; D011247:Pregnancy; D011248:Pregnancy Complications; D011270:Pregnancy, Animal; D012039:Regional Blood Flow; D012756:Sheep; D055988:Uterine Artery / Q000378:metabolism*; D014599:Uterus / Q000098:blood supply*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism
D042461:Vascular Endothelial Growth Factor A