ELABELA Deficiency Promotes Preeclampsia and Cardiovascular Malformations in Mice
LENA HO WAI MUN MARIE VAN DIJK SAM TAN JIAN CHYE DANIEL M MESSERSCHIMDT SERENE CHNG SHEENA ONG LING KA YI SOUAD BOUSSATA GRACE GOH HUI YI GJIS B AFINK
MARIE VAN DIJK
SAM TAN JIAN CHYE
DANIEL M MESSERSCHIMDT
SERENE CHNG
SHEENA ONG
LING KA YI
SOUAD BOUSSATA
GRACE GOH HUI YI
GJIS B AFINK
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Alternative Title
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.
Keywords
Peptides, Hormones, Pregnancy, Cardiovascular
Source Title
Science
Publisher
American Association for the Advancement of Science
Series/Report No.
Collections
Rights
Attribution-NonCommercial 4.0 International
Date
2017-08-18
DOI
10.1126/science.aam6607
Type
Article