Pravastatin induces placental growth factor (PGF) and ameliorates preeclampsia in a mouse model

K Kumasawa, M Ikawa, H Kidoya… - Proceedings of the …, 2011 - National Acad Sciences
K Kumasawa, M Ikawa, H Kidoya, H Hasuwa, T Saito-Fujita, Y Morioka, N Takakura…
Proceedings of the National Academy of Sciences, 2011National Acad Sciences
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 …
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.
National Acad Sciences