Effect of recombinant placental growth factor 2 on hypertension induced by full-length mouse soluble fms-like tyrosine kinase 1 adenoviral vector in pregnant mice.
The first aim of our study was to develop a pregnant mouse model for preeclampsia using adenoviral vector containing mouse full-length soluble fms-like tyrosine kinase 1 (sFlt-1) but not truncated sFlt-1. The second aim was to evaluate effects of recombinant mouse (rm) vascular endothelial growth factor (VEGF) and rm placental growth factor (PlGF) on a preeclampsia model induced by adenoviral vector containing mouse full-length sFlt-1. We injected adenoviral vector containing mouse full-length sFlt-1 on day 8.5 or 9.5 of gestation into pregnant Institute of Cancer Research mice, resulting in hypertension, proteinuria, and similar glomerular histological changes as those seen in human preeclamptic women with glomerular endotheliosis on day 16.5 or 17.5 of gestation. The preeclampsia models were treated with 100 microg/kg of rmVEGF164 (n=5), 100 microg/kg of rmPlGF-2 (n=5), or vehicle (n=7) twice a day for 2 days IP. The rmVEGF164 treatment significantly decreased the mean blood pressure on day 16.5 or 17.5 of gestation compared with the vehicle treatment (85+/-4 versus 97+/-2 mm Hg; P=0.018). The rmPlGF-2 treatment also significantly decreased the mean blood pressure on day 16.5 or 17.5 of gestation compared with the vehicle treatment (86+/-3 versus 97+/-2 mm Hg; P=0.018). However, proteinuria was not affected by either rmVEGF164 or rmPlGF-2. In conclusion, we, for the first time, created a mouse preeclampsia model using mouse full-length sFlt-1. VEGF and PlGF may be promising for ameliorating hypertension in women with preeclampsia. Additional study of PlGF as a potential drug for preeclampsia is warranted.
Department of Obstetrics and Gynecology, Jichi Medical University School of Medicine, Tochigi, Japan.
Hirotada
H
Suzuki
Akihide
A
Ohkuchi
Shigeki
S
Matsubara
Yuji
Y
Takei
Masato
M
Murakami
Masabumi
M
Shibuya
Mitsuaki
M
Suzuki
Yasufumi
Y
Sato
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005822:Genetic Vectors; D006801:Humans; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy*; D008565:Membrane Proteins / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D000072483:Placenta Growth Factor; D011225:Pre-Eclampsia / Q000139:chemically induced / Q000188:drug therapy*; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000494:pharmacology*; D011270:Pregnancy, Animal; D011336:Probability; D011507:Proteinuria; D011897:Random Allocation; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000494:pharmacology*; D012016:Reference Values; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology
D008565:Membrane Proteins; C000608036:PGF protein, human; C098069:PIGF protein, human; C000608037:Pgf protein, mouse; D011257:Pregnancy Proteins; D042461:Vascular Endothelial Growth Factor A; D000072483:Placenta Growth Factor; D051496:Receptor, Fibroblast Growth Factor, Type 1