TY - JOUR
T1 - Pravastatin induces placental growth factor (PGF) and ameliorates preeclampsia in a mouse model
AU - Kumasawa, Keiichi
AU - Ikawa, Masahito
AU - Kidoya, Hiroyasu
AU - Hasuwa, Hidetoshi
AU - Saito-Fujita, Tomoko
AU - Morioka, Yuka
AU - Takakura, Nobuyuki
AU - Kimura, Tadashi
AU - Okabe, Masaru
PY - 2011/1/25
Y1 - 2011/1/25
N2 - 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.
AB - 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.
KW - 3-hydroxy-3-methyl-glutaryl-CoA
KW - Hemolytic anemia, elevated liver enzymes, and low platelet count
KW - Trophoblast
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U2 - 10.1073/pnas.1011293108
DO - 10.1073/pnas.1011293108
M3 - Article
C2 - 21187414
AN - SCOPUS:79952145885
SN - 0027-8424
VL - 108
SP - 1451
EP - 1455
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 4
ER -