TY - JOUR
T1 - ELABELA deficiency promotes preeclampsia and cardiovascular malformations in mice
AU - Ho, Lena
AU - Van Dijk, Marie
AU - Chye, Sam Tan Jian
AU - Messerschmidt, Daniel M.
AU - Chng, Serene C.
AU - Ong, Sheena
AU - Yi, Ling Ka
AU - Boussata, Souad
AU - Goh, Grace Hui Yi
AU - Afink, Gijs B.
AU - Lim, Chin Yan
AU - Dunn, N. Ray
AU - Solter, Davor
AU - Knowles, Barbara B.
AU - Reversade, Bruno
PY - 2017/8/18
Y1 - 2017/8/18
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85021804387&partnerID=8YFLogxK
U2 - 10.1126/science.aam6607
DO - 10.1126/science.aam6607
M3 - Article
C2 - 28663440
AN - SCOPUS:85021804387
VL - 357
SP - 707
EP - 713
JO - Science
JF - Science
SN - 0036-8075
IS - 6352
ER -