title: Pravastatin induces placental growth factor (PGF) and ameliorates preeclampsia in a mouse model.
abstract: Preeclampsia is a relatively common pregnancy-related disorder. Both maternal and fetal lives will be endangered if it proceeds unabated. Recently, the placenta-derived anti-angiogenic factors, such as soluble fms-like tyrosine kinase-1 (sFLT1) and soluble endoglin (sENG), have attracted attention in the progression of preeclampsia. Here, we established a unique experimental model to test the role of sFLT1 in preeclampsia using a lentiviral vector-mediated placenta-specific expression system. The model mice showed hypertension and proteinuria during pregnancy, and the symptoms regressed after parturition. Intrauterine growth restriction was also observed. We further showed that pravastatin induced the VEGF-like angiogenic factor placental growth factor (PGF) and ameliorated the symptoms. We conclude that our experimental preeclamptic murine model phenocopies the human case, and the model identifies low-dose statins and PGF as candidates for preeclampsia treatment.
authors.affiliation: Department of Experimental Genome Research, Research Institute for Microbial Diseases, Osaka University, Suita 565-0871, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Kumasawa
authors.forename: Masahito
authors.initials: M
authors.lastname: Ikawa
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Kidoya
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Hasuwa
authors.forename: Tomoko
authors.initials: T
authors.lastname: Saito-Fujita
authors.forename: Yuka
authors.initials: Y
authors.lastname: Morioka
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Takakura
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kimura
authors.forename: Masaru
authors.initials: M
authors.lastname: Okabe
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002460:Cell Line; D004195:Disease Models, Animal; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D016086:Lentivirus / Q000235:genetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010920:Placenta / Q000378:metabolism; D000072483:Placenta Growth Factor; D017035:Pravastatin / Q000008:administration & dosage / Q000494:pharmacology*; D011225:Pre-Eclampsia / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000235:genetics / Q000378:metabolism*; D014161:Transduction, Genetic; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics / Q000378:metabolism
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C000608036:PGF protein, human; C000608037:Pgf protein, mouse; D011257:Pregnancy Proteins; D000072483:Placenta Growth Factor; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1; D017035:Pravastatin