ELABELA deficiency promotes preeclampsia and cardiovascular malformations in mice

Lena Ho*, Marie Van Dijk, Sam Tan Jian Chye, Daniel M. Messerschmidt, Serene C. Chng, Sheena Ong, Ling Ka Yi, Souad Boussata, Grace Hui Yi Goh, Gijs B. Afink, Chin Yan Lim, N. Ray Dunn, Davor Solter, Barbara B. Knowles, Bruno Reversade

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)707-713
Number of pages7
JournalScience
Volume357
Issue number6352
DOIs
Publication statusPublished - 18 Aug 2017

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