Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia.
Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia.
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DOI：
10.1097/01.ogx.0000083700.80693.da
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发表时间：
2003-09
期刊：
影响因子：
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通讯作者：
S. Maynard;J. Min;J. Merchan;K. Lim;Jianyi Li;S. Mondal;T. Libermann;James P. Morgon;F. Sellke-F
中科院分区：
文献类型：
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作者：
S. Maynard;J. Min;J. Merchan;K. Lim;Jianyi Li;S. Mondal;T. Libermann;James P. Morgon;F. Sellke-F
子痫前期会影响5％的妊娠综合征，导致孕产妇和胎儿的发病率和死亡率。先兆子痫的病理生理仍然很大未知。据推测，胎盘缺血是早期事件，导致胎盘产生可溶性因子或导致母体内皮功能障碍的因素，从而导致高血压，蛋白尿和水肿的临床发现。在这里，我们确认胎盘可溶性FMS样酪氨酸激酶1（SFLT1）是VEGF和胎盘生长因子（PLGF）的拮抗剂（PLGF），在先兆子痫中被上调，导致分娩后下降的SFLT1的系统水平升高。我们证明，先兆子痫患者的循环SFLT1增加与循环水平降低相关，自由VEGF和PLGF水平降低，导致体外内皮功能障碍，可以通过外源性VEGF和PLGF营救。此外，VEGF和PLGF在体外引起大鼠肾动脉的微血管松弛，该小动脉被SFLT1阻塞。最后，对怀孕大鼠的SFLT1给药会诱导高血压，蛋白尿和肾小球内皮病，这是先兆子痫的经典病变。这些观察结果表明，过多的循环SFLT1有助于先兆子痫的发病机理。
Preeclampsia, a syndrome affecting 5% of pregnancies, causes substantial maternal and fetal morbidity and mortality. The pathophysiology of preeclampsia remains largely unknown. It has been hypothesized that placental ischemia is an early event, leading to placental production of a soluble factor or factors that cause maternal endothelial dysfunction, resulting in the clinical findings of hypertension, proteinuria, and edema. Here, we confirm that placental soluble fms-like tyrosine kinase 1 (sFlt1), an antagonist of VEGF and placental growth factor (PlGF), is upregulated in preeclampsia, leading to increased systemic levels of sFlt1 that fall after delivery. We demonstrate that increased circulating sFlt1 in patients with preeclampsia is associated with decreased circulating levels of free VEGF and PlGF, resulting in endothelial dysfunction in vitro that can be rescued by exogenous VEGF and PlGF. Additionally, VEGF and PlGF cause microvascular relaxation of rat renal arterioles in vitro that is blocked by sFlt1. Finally, administration of sFlt1 to pregnant rats induces hypertension, proteinuria, and glomerular endotheliosis, the classic lesion of preeclampsia. These observations suggest that excess circulating sFlt1 contributes to the pathogenesis of preeclampsia.