ELABELA deficiency promotes preeclampsia and cardiovascular malformations in mice - PubMed

Affiliations

• PMID: 28663440
• DOI: 10.1126/science.aam6607

ELABELA deficiency promotes preeclampsia and cardiovascular malformations in mice

Lena Ho et al. Science. 2017.

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.

Comment in

• Circulating peptide prevents preeclampsia.

  Wirka RC, Quertermous T. Wirka RC, et al. Science. 2017 Aug 18;357(6352):643-644. doi: 10.1126/science.aao2642. Science. 2017. PMID: 28818928 No abstract available.

• A Tale of Two Elabela Null Mice.

  Papangeli I, Chun HJ. Papangeli I, et al. Trends Endocrinol Metab. 2017 Nov;28(11):759-760. doi: 10.1016/j.tem.2017.09.004. Epub 2017 Sep 27. Trends Endocrinol Metab. 2017. PMID: 28964631 Free PMC article.

Similar articles

• ELABELA, as a potential diagnostic biomarker of preeclampsia, regulates abnormally shallow placentation via APJ.

  Zhou L, Sun H, Cheng R, Fan X, Lai S, Deng C. Zhou L, et al. Am J Physiol Endocrinol Metab. 2019 May 1;316(5):E773-E781. doi: 10.1152/ajpendo.00383.2018. Epub 2019 Mar 12. Am J Physiol Endocrinol Metab. 2019. PMID: 30860880

• Elabela and Apelin actions in healthy and pathological pregnancies.

  Eberlé D, Marousez L, Hanssens S, Knauf C, Breton C, Deruelle P, Lesage J. Eberlé D, et al. Cytokine Growth Factor Rev. 2019 Apr;46:45-53. doi: 10.1016/j.cytogfr.2019.03.003. Epub 2019 Mar 16. Cytokine Growth Factor Rev. 2019. PMID: 30910349 Review.

• The Apelinergic System in Pregnancy.

  Pécheux O, Correia-Branco A, Cohen M, Martinez de Tejada B. Pécheux O, et al. Int J Mol Sci. 2023 Apr 28;24(9):8014. doi: 10.3390/ijms24098014. Int J Mol Sci. 2023. PMID: 37175743 Free PMC article. Review.

• Peptide hormone ELABELA enhances extravillous trophoblast differentiation, but placenta is not the major source of circulating ELABELA in pregnancy.

  Georgiadou D, Boussata S, Ranzijn WHM, Root LEA, Hillenius S, Bij de Weg JM, Abheiden CNH, de Boer MA, de Vries JIP, Vrijkotte TGM, Lambalk CB, Kuijper EAM, Afink GB, van Dijk M. Georgiadou D, et al. Sci Rep. 2019 Dec 13;9(1):19077. doi: 10.1038/s41598-019-55650-5. Sci Rep. 2019. PMID: 31836787 Free PMC article.

• The biological function of ELABELA and APJ signaling in the cardiovascular system and pre-eclampsia.

  Liu Y, Wang L, Shi H. Liu Y, et al. Hypertens Res. 2019 Jul;42(7):928-934. doi: 10.1038/s41440-018-0193-3. Epub 2019 Jan 9. Hypertens Res. 2019. PMID: 30626933 Review.

Cited by

• Animal models of preeclampsia: investigating pathophysiology and therapeutic targets.

  Bakrania BA, George EM, Granger JP. Bakrania BA, et al. Am J Obstet Gynecol. 2022 Feb;226(2S):S973-S987. doi: 10.1016/j.ajog.2020.10.025. Epub 2021 Mar 12. Am J Obstet Gynecol. 2022. PMID: 33722383 Free PMC article. Review.

• Serum lncRNAs in early pregnancy as potential biomarkers for the prediction of pregnancy-induced hypertension, including preeclampsia.

  Dai C, Zhao C, Xu M, Sui X, Sun L, Liu Y, Su M, Wang H, Yuan Y, Zhang S, Shi J, Sun J, Li Y. Dai C, et al. Mol Ther Nucleic Acids. 2021 Mar 17;24:416-425. doi: 10.1016/j.omtn.2021.03.010. eCollection 2021 Jun 4. Mol Ther Nucleic Acids. 2021. PMID: 33868785 Free PMC article.

• The apelinergic system: a perspective on challenges and opportunities in cardiovascular and metabolic disorders.

  Marsault E, Llorens-Cortes C, Iturrioz X, Chun HJ, Lesur O, Oudit GY, Auger-Messier M. Marsault E, et al. Ann N Y Acad Sci. 2019 Nov;1455(1):12-33. doi: 10.1111/nyas.14123. Epub 2019 Jun 25. Ann N Y Acad Sci. 2019. PMID: 31236974 Free PMC article. Review.

• Noncanonical microprotein regulation of immunity.

  Nichols C, Do-Thi VA, Peltier DC. Nichols C, et al. Mol Ther. 2024 Sep 4;32(9):2905-2929. doi: 10.1016/j.ymthe.2024.05.021. Epub 2024 May 11. Mol Ther. 2024. PMID: 38734902 Review.

• Analysis of Placental Arteriovenous Formation Reveals New Insights Into Embryos With Congenital Heart Defects.

  Kalisch-Smith JI, Morris EC, Strevens MAA, Redpath AN, Klaourakis K, Szumska D, Outhwaite JE, Sun X, Vieira JM, Smart N, De Val S, Riley PR, Sparrow DB. Kalisch-Smith JI, et al. Front Genet. 2022 Jan 19;12:806136. doi: 10.3389/fgene.2021.806136. eCollection 2021. Front Genet. 2022. PMID: 35126469 Free PMC article.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Atypon
  • Ovid Technologies, Inc.

• Other Literature Sources

  • The Lens - Patent Citations Database
  • scite Smart Citations

• Molecular Biology Databases

  • BioCyc
  • Gene Ontology
  • GlyGen glycoinformatics resource
  • Mouse Genome Informatics (MGI)