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Science. 2017 Aug 18;357(6352):707-713. doi: 10.1126/science.aam6607. Epub 2017 Jun 29.

ELABELA deficiency promotes preeclampsia and cardiovascular malformations in mice.

Author information

1
Institute of Medical Biology, A*STAR, 8A Biomedical Grove, Immunos, Singapore 138648. lena.ho@reversade.com bruno@reversade.com.
2
Reproductive Biology Laboratory, Obstetrics and Gynaecology, Academic Medical Center (AMC), Meibergdreef 9, 1105 AZ Amsterdam-Zuidoost, Netherlands.
3
Institute of Medical Biology, A*STAR, 8A Biomedical Grove, Immunos, Singapore 138648.
4
Institute of Molecular and Cell Biology, A*STAR, 61 Biopolis Drive, Proteos, Singapore 138673.
5
National University of Singapore, Department of Paediatrics, 1E Kent Ridge Road, Singapore 119228.
6
Medical Genetics Department, KoƧ University School of Medicine, 34010 Istanbul, Turkey.

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.

PMID:
28663440
DOI:
10.1126/science.aam6607
[Indexed for MEDLINE]

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