Elabela
ELA, Toddler, APELA gene product, ELA-32, apelin receptor early endogenous ligand
Elabela, also called Toddler or APELA, is the second endogenous ligand of the apelin receptor, discovered in 2013 and 2014 in what had been annotated as a non-coding region of the genome. It is essential for heart development in zebrafish and is expressed in adult human heart, vasculature, kidney and placenta. Human evidence remains entirely descriptive.
Mechanism
The APELA gene encodes a 54-residue preproprotein with a 22-residue signal sequence, yielding the 32-residue mature peptide ELA-32, which is further processed to ELA-21 and ELA-11. Elabela shares no sequence homology with apelin yet activates the same receptor, APJ (APLNR), a class A GPCR coupling to Gi/Go with beta-arrestin recruitment. Signalling profiles are not identical: elabela and apelin show different degrees of bias between G protein and beta-arrestin pathways at APJ, which may explain divergent downstream effects in some systems.
Developmentally, elabela is the earlier ligand, expressed before apelin, and its deletion in zebrafish causes severe cardiac morphogenesis defects with rudimentary or absent hearts. In adults the peptide is prominent in vascular endothelium and kidney, where it produces nitric oxide-dependent vasodilatation, and in placenta, where reduced expression has been repeatedly associated with pre-eclampsia. Elabela expression is downregulated in human pulmonary arterial hypertension, and exogenous administration in animal models partially compensates for this loss.
What the research shows
The key adult cardiovascular paper established elabela as a genuine endogenous APJ agonist outside development. It demonstrated expression in adult human cardiovascular tissue, showed the peptide is downregulated in pulmonary arterial hypertension, and reported that exogenous administration compensated for that loss in disease models. A recommendation followed from IUPHAR to formally recognise elabela as a second endogenous ligand of the apelin receptor.
Metabolic work has clarified why translation is hard. Synthetic ELA-32 incubated with human plasma and kidney homogenate is degraded quickly, and validating endogenous quantification by ELISA proved to require careful mass spectrometry cross-checking, because several commercial assays measure fragments or cross-react. Associations reported between low circulating elabela and pre-eclampsia should therefore be treated cautiously until assay performance is settled. No interventional human study of elabela has been registered or reported.
Evidence assessment
Preclinical only
There are no clinical trials of elabela, registered or reported. Every surviving citation is a tissue expression study, a receptor pharmacology paper, an in vitro metabolism study or a nomenclature review. Human data comprise expression measurements and ex vivo vessel work only; all efficacy evidence is from animal models.
Tiers are applied consistently across the library and re-checked when new trials read out. Read the grading method.
Key studies
Elabela/Toddler Is an Endogenous Agonist of the Apelin APJ Receptor in the Adult Cardiovascular System, and Exogenous Administration of the Peptide Compensates for the Downregulation of Its Expression in Pulmonary Arterial Hypertension Preclinical only
Confirmed elabela as an adult cardiovascular APJ agonist, showed downregulation in pulmonary arterial hypertension and partial compensation with exogenous peptide in animal models.
In vitro metabolism of synthetic Elabela/Toddler (ELA-32) peptide in human plasma and kidney homogenates analyzed with mass spectrometry and validation of endogenous peptide quantification in tissues by ELISA Preclinical only
ELA-32 is rapidly metabolised in human plasma and kidney; several commercial immunoassays require validation before circulating elabela measurements can be trusted.
International Union of Basic and Clinical Pharmacology. CVII. Structure and Pharmacology of the Apelin Receptor with a Recommendation that Elabela/Toddler Is a Second Endogenous Peptide Ligand of the Apelin Receptor Preclinical only
Formally recommended recognition of elabela as a second endogenous apelin receptor ligand and set out the comparative pharmacology.
Safety
No human safety data exist. Elabela has never been administered to people in a published study. The predicted pharmacology, systemic vasodilatation and blood pressure reduction, carries obvious hazard outside a monitored setting, and roles in angiogenesis and placental biology mean it is entirely unsuitable for use in pregnancy or by anyone outside a formal study.
Regulatory status
| Jurisdiction | Status |
|---|---|
| United Kingdom | No UK marketing authorisation. Unlicensed substance; supply for human consumption would breach the Human Medicines Regulations 2012. |
| United States | No FDA approval and no registered clinical trial. Available only as a research reagent, explicitly not for human use. |
| WADA (sport) | Not individually named on the WADA Prohibited List. Captured by section S0 as a substance with no approval from any governmental regulatory health authority for human therapeutic use, prohibited at all times. |
Questions
They share no sequence similarity yet activate the same receptor. Elabela appears earlier in development, is essential for heart formation in zebrafish, and shows a different balance of G protein versus beta-arrestin signalling at APJ.
No. There are no registered or published interventional human studies. Everything known in people comes from measuring the peptide in tissue and blood, or testing it on isolated human vessels.