Soluble endoglin contributes to the pathogenesis of preeclampsia
Soluble endoglin contributes to the pathogenesis of preeclampsia
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DOI：
10.1038/nm1429
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发表时间：
2006-06-01
期刊：
影响因子：
82.9
通讯作者：
Karumanchi, S. Ananth
中科院分区：
文献类型：
--
作者：
Venkatesha, Shivalingappa;Toporsian, Mourad;Karumanchi, S. Ananth
子痫前期是一种妊娠期特有的高血压综合征，可引起母体和胎儿的大量发病率和死亡率。过量胎盘源性可溶性VEGF受体1 （sVEGFR1或sFlt1）介导的母体内皮功能障碍正在成为疾病发病机制中的一个重要组成部分。我们报道了一种新的胎盘来源的可溶性tgf - β辅助受体内啡肽（sEng），它在子痫前期个体的血清中升高，与疾病严重程度和分娩后下降相关。sEng在体外抑制毛细血管的形成，在体内诱导血管通透性和高血压。sFlt1在妊娠大鼠中的作用被放大，导致严重的子痫前期，包括HELLP（溶血、肝酶升高、血小板降低）综合征和胎儿生长受限。sEng损害tgf - β 1与其受体的结合和下游信号传导，包括对eNOS激活和血管舒张的影响，表明sEng导致血管中tgf - β信号传导失调。我们的研究结果表明，sEng可能与sFlt1协同作用，诱导严重的先兆子痫。
Preeclampsia is a pregnancy-specific hypertensive syndrome that causes substantial maternal and fetal morbidity and mortality. Maternal endothelial dysfunction mediated by excess placenta-derived soluble VEGF receptor 1 ( sVEGFR1 or sFlt1) is emerging as a prominent component in disease pathogenesis. We report a novel placenta-derived soluble TGF-beta coreceptor, endoglin ( sEng), which is elevated in the sera of preeclamptic individuals, correlates with disease severity and falls after delivery. sEng inhibits formation of capillary tubes in vitro and induces vascular permeability and hypertension in vivo. Its effects in pregnant rats are amplified by coadministration of sFlt1, leading to severe preeclampsia including the HELLP ( hemolysis, elevated liver enzymes, low platelets) syndrome and restriction of fetal growth. sEng impairs binding of TGF-beta 1 to its receptors and downstream signaling including effects on activation of eNOS and vasodilation, suggesting that sEng leads to dysregulated TGF-beta signaling in the vasculature. Our results suggest that sEng may act in concert with sFlt1 to induce severe preeclampsia.