Transient local overexpression of human vascular endothelial growth factor (VEGF) in mouse feto-maternal interface during mid-term pregnancy lowers systemic maternal blood pressure.
The effect on maternal circulation of transient human vascular endothelial growth factor (VEGF) (165) cDNA transfection into the mouse feto-maternal interface at day 14.5 post coitus (p.c.) using a hemagglutinating virus of Japan-envelope (HVJ-E) vector system is reported. On day 15.5 p.c., Western blotting clearly showed overexpression of 18 kD VEGF protein in the uterus. After VEGF transfection, the blood pressure was significantly lowered for 48 hours. On day 17.5 p.c., the blood pressure returned to the control level. Proteinuria was not observed after VEGF transfection. No preterm birth was observed during the course of pregnancy after the transfection procedure. After 24 hours of transfection, human VEGF was not detectable and the mouse VEGF level was similar to that in peripheral blood. However, the soluble fms-like tyrosine kinase (Flt)-1 concentration was significantly lower in VEGF-transfected mice. These results suggest that extraamniotic VEGF overexpression lowered the systemic blood pressure without altering the VEGF concentration in the peripheral blood. Local overexpression of VEGF may become a novel treatment for pregnancy-related disorders such as hypertension complicated-pregnancy and preeclampsia.
Koyama
S
S
Division of Obstetrics and Gynecology, Osaka University Graduate School of Medicine 2-2, Yamadaoka, Suita, Osaka 5650871, Japan.
Kimura
T
T
Ogita
K
K
Nakamura
H
H
Khan
Md A H N Ali
MA
Yoshida
S
S
Watanabe
M
M
Shimoya
K
K
Kaneda
Y
Y
Murata
Y
Y
D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D015153:Blotting, Western; D018076:DNA, Complementary / Q000493:pharmacokinetics; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008297:Male; D051379:Mice; D021041:Placental Circulation / Q000502:physiology*; D011225:Pre-Eclampsia / Q000503:physiopathology / Q000628:therapy*; D011247:Pregnancy; D011507:Proteinuria / Q000503:physiopathology / Q000628:therapy; D014162:Transfection; D014599:Uterus / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000097:blood / Q000235:genetics*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood
D018076:DNA, Complementary; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C501163:Flt1 protein, mouse; D040281:Vascular Endothelial Growth Factor Receptor-1