Proceedings of the National Academy of Sciences · 2010 · 361 citations · 34 references
MedicineObstetricsPharmacologyMaternal-fetal MedicineReproductive EndocrinologyReproductive ImmunologyHypertensive DisordersIntrauterine Growth RestrictionMaternal-fetal PhysiologyPlacental PhysiologyPregnancyPregnancy-induced HypertensionExperimental Model TestingLentiviral Vector TransductionMurine ModelsPlacental Growth Factor SignalingPreeclampsia PathophysiologyPregnancy-related Blood Pressure RegulationPregnancy-related HypertensionPregnancy-related Pharmacotherapy
Preeclampsia is a common, life‑threatening pregnancy disorder linked to placenta‑derived anti‑angiogenic factors such as sFLT1 and sENG. The study aimed to test the role of sFLT1 in preeclampsia by creating a placenta‑specific overexpression model. The authors used a lentiviral vector‑mediated system to drive sFLT1 expression specifically in the placenta. The resulting mice exhibited hypertension, proteinuria, and intrauterine growth restriction that resolved after delivery, and pravastatin treatment raised placental growth factor levels, alleviating symptoms and indicating low‑dose statins and PGF as potential therapies.
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.
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Sharon E. Maynard, Jiang-Yong Min, Jaime R. Merchan et al. · Journal of Clinical Investigation · 2003 · 4K citations · Full text
Circulating Angiogenic Factors and the Risk of Preeclampsia
Richard J. Levine, Cong Qian, Lucinda J. England et al. · New England Journal of Medicine · 2004 · 3.6K citations · Full text
Circulating angiogenic factors and the risk of preeclampsia*
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Medicine, Gynecology, Obstetrics +14
Soluble endoglin contributes to the pathogenesis of preeclampsia
Shivalingappa Venkatesha, Mourad Toporsian, Chun Sing Lam et al. · Nature Medicine · 2006 · 1.8K citations
Soluble Endoglin and Other Circulating Antiangiogenic Factors in Preeclampsia
Richard J. Levine, Chun Sing Lam, Cong Qian et al. · New England Journal of Medicine · 2006 · 1.8K citations · Full text