journal article·2026-06Open access

ELABELA Targets Mitochondria to Modulate Heart Development

Jian Wang, Qingjie Wang, Zhikang Xu, Shuang Zhou, Yue Zhou, Junjie Yang, Lingfeng Tong, Zhuo Meng, Mei Yang, Wen Zhao, Tie Yang, Hualin Wang, Jun Zhang, Rubin Tan, Lei Wang, Yuqiang Huang, Bin Zhou, Sun Chen, Bing Zhang, Jinxiang Yuan, Jianyuan Zhao, Alex F. Chen, Kun Sun

Advanced Science· Volume 13· Issue 33

Abstract

ABSTRACT Congenital heart disease (CHD) is a leading cause of neonatal morbidity and mortality, whose underlying pathogenesis remains largely unclear, and lacks reliable biomarkers or therapeutic targets for early detection and treatment during pregnancy. In this study, we investigated the role of endogenous peptide ELABELA (ELA) in fetal CHD. Our findings reveal that ELA levels are significantly reduced in human fetal cardiac tissues with CHD. In mouse models, ELA deletion in cardiac progenitor cells disrupted mitochondrial function, directly contributing to cardiac malformations. Mechanistically, ELA deficiency caused mitochondrial swelling by inhibiting the APJ‐AKT‐BCL2/BAX signaling pathway. Notably, exogenous ELA administration reduced both CHD severity and incidence in mice. Furthermore, plasma ELA levels were markedly down‐regulated in human pregnancies with fetal CHD. These findings establish ELA as a crucial regulator of cardiac development and highlight its potential as both a biomarker and therapeutic target for the prevention and management of fetal CHD during gestation.
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Research context

OpenAlex topics: Apelin-related biomedical research · Cardiovascular, Neuropeptides, and Oxidative Stress Research · Pregnancy-related medical research

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Pediatric Cardiology Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine Shanghai China

Institute for Developmental and Regenerative Cardiovascular Medicine Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine Shanghai China

Engineering Research Center of Medical Devices For Congenital Heart Disease Ministry of Education Xinhua Hospital Shanghai Jiao Tong University School of Medicine Shanghai China

Department of Cardiology Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine Shanghai China

Ministry of Education‐Shanghai Key Laboratory of Children's Environmental Health Xinhua Hospital Shanghai Jiao Tong University School of Medicine Shanghai China

Department of Physiology Basic Medical School Southwest Medical University Luzhou Sichuan China

Diagnosis and Treatment Center For In Utero Pediatric Diseases Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai China

Linyi Maternal and Child Health Care Hospital Linyi Shandong China

New Cornerstone Science Laboratory State Key Laboratory of Cell Biology Shanghai Institute of Biochemistry and Cell Biology Center For Excellence in Molecular Cell Science Chinese Academy of Sciences University of Chinese Academy of Sciences Shanghai China

Lin He's Academician Workstation of New Medicine and Clinical Translation Jining Medical University Jining Shandong China

Funding

National Natural Science Foundation of China · Natural Science Foundation of Shanghai Municipality · School of Medicine, Shanghai Jiao Tong University

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