Pravastatin induces placental growth factor (PGF) and ameliorates preeclampsia in a mouse model
Pravastatin induces placental growth factor (PGF) and ameliorates preeclampsia in a mouse model
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DOI：
10.1073/pnas.1011293108
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发表时间：
2011-01-25
影响因子：
11.1
通讯作者：
Okabe, Masaru
中科院分区：
文献类型：
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作者：
Kumasawa, Keiichi;Ikawa, Masahito;Okabe, Masaru
先兆子痫是一种相对常见的妊娠相关疾病。如果继续下去，母亲和胎儿的生命都将受到威胁。近年来，胎盘源性抗血管生成因子，如可溶性fms样酪氨酸激酶-1（sFLT 1）和可溶性内皮糖蛋白（sENG）在子痫前期的发生发展中的作用引起了人们的关注。在这里，我们建立了一个独特的实验模型，使用慢病毒载体介导的胎盘特异性表达系统来测试sFLT 1在先兆子痫中的作用。模型小鼠在妊娠期出现高血压和蛋白尿，分娩后症状消退。还观察到宫内生长受限。我们进一步表明，普伐他汀诱导VEGF样血管生成因子胎盘生长因子（PGF）和改善症状。我们的结论是，我们的实验性先兆子痫小鼠模型表型模仿人类的情况下，该模型确定低剂量他汀类药物和PGF作为先兆子痫治疗的候选人。
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.