ELABELA deficiency promotes preeclampsia and cardiovascular malformations in mice
ELABELA deficiency promotes preeclampsia and cardiovascular malformations in mice
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DOI：
10.1126/science.aam6607
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发表时间：
2017-08-18
期刊：
影响因子：
56.9
通讯作者：
Reversade, Bruno
中科院分区：
文献类型：
--
作者：
Ho, Lena;van Dijk, Marie;Reversade, Bruno
先兆子痫 (PE) 是一种妊娠高血压综合征，影响 5% 至 8% 的妊娠。尽管PE是胎儿和孕产妇发病和死亡的主要原因，但其分子病因学仍不清楚。在这里，我们证明 ELABELA (ELA) 是 apelin 受体（APLNR 或 APJ）的内源性配体，是胎盘分泌的循环激素。 Elabela 但 Apelin 基因敲除怀孕小鼠表现出类似 PE 的症状，包括蛋白尿和由于胎盘血管生成缺陷导致的血压升高。在小鼠中，输注外源性 ELA 可使高血压、蛋白尿和出生体重正常化。 ELA 在人类胎盘中含量丰富，可增加滋养层样细胞的侵袭性，表明它可增强胎盘发育以预防 PE。 ELA-APLNR 信号轴可能为治疗常见妊娠相关并发症（包括 PE）提供新的范例。
Preeclampsia (PE) is a gestational hypertensive syndrome affecting between 5 and 8% of all pregnancies. Although PE is the leading cause of fetal and maternal morbidity and mortality, its molecular etiology is still unclear. Here, we show that ELABELA (ELA), an endogenous ligand of the apelin receptor (APLNR, or APJ), is a circulating hormone secreted by the placenta. Elabela but not Apelin knockout pregnant mice exhibit PE-like symptoms, including proteinuria and elevated blood pressure due to defective placental angiogenesis. In mice, infusion of exogenous ELA normalizes hypertension, proteinuria, and birth weight. ELA, which is abundant in human placentas, increases the invasiveness of trophoblast-like cells, suggesting that it enhances placental development to prevent PE. The ELA-APLNR signaling axis may offer a new paradigm for the treatment of common pregnancy-related complications, including PE.