Apelin and Elabela/Toddler; double ligands for APJ/Apelin receptor in heart development, physiology, and pathology

Keiji Kuba, Teruki Sato, Yumiko Imai, Tomokazu Yamaguchi

Research output: Contribution to journalReview articlepeer-review

67 Citations (Scopus)


Apelin is an endogenous peptide ligand for the G protein-coupled receptor APJ/AGTRL1/APLNR and is widely expressed throughout human body. In adult hearts Apelin-APJ/Apelin receptor axis is potently inotropic, vasodilatory, and pro-angiogenic and thereby contributes to maintaining homeostasis in normal and pathological hearts. Apelin-APJ/Apelin receptor is also involved in heart development including endoderm differentiation, heart morphogenesis, and coronary vascular formation. APJ/Apelin receptor had been originally identified as an orphan receptor for its sequence similarity to Angiotensin II type 1 receptor, and it was later deorphanized by identification of Apelin in 1998. Both Apelin and Angiotensin II are substrates for Angiotensin converting enzyme 2 (ACE2), which degrades the peptides and thus negatively regulates their agonistic activities. Elabela/Toddler, which shares little sequence homology with Apelin, has been recently identified as a second endogenous APJ ligand. Elabela plays crucial roles in heart development and disease conditions presumably at time points or at areas of the heart different from Apelin. Apelin and Elabela seem to constitute a spatiotemporal double ligand system to control APJ/Apelin receptor signaling in the heart. These expanding knowledges of Apelin systems would further encourage therapeutic applications of Apelin, Elabela, or their synthetic derivatives for cardiovascular diseases.

Original languageEnglish
Pages (from-to)62-70
Number of pages9
Publication statusPublished - Jan 2019
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Physiology
  • Endocrinology
  • Cellular and Molecular Neuroscience


Dive into the research topics of 'Apelin and Elabela/Toddler; double ligands for APJ/Apelin receptor in heart development, physiology, and pathology'. Together they form a unique fingerprint.

Cite this