Elabela
The embryonic signal that turned out to be a second key for the apelin receptor
Elabela, also called Toddler or Apela, is a short peptide hormone discovered when a stretch of the genome thought not to code for protein turned out to make one. It activates the apelin receptor, like apelin, and is needed for normal heart and blood vessel development in the embryo. In rodents it eased hypertensive heart damage, heart attack injury and pulmonary hypertension. In people it has only been measured in blood, with lower levels reported in heart failure, atrial fibrillation and kidney disease.
No established human dose Details ↓
Recommended Dosing
No established human dose
Elabela has never been given to people in any study we read. Its human evidence is measurement only: plasma and serum levels compared across heart failure, hypertension, atrial fibrillation, chronic kidney disease and preeclampsia, with results that conflict for preeclampsia.
What is it?
In 2014 a zebrafish study screening for unrecognised signalling proteins in the embryo identified a short, conserved, secreted peptide it called Toddler. Embryos lacking it, or making too much, moved their cells poorly during gastrulation. Toddler worked by activating the apelin receptor, until then known only as the receptor for apelin. The gene had been classed as non-coding in fish and human genomes. Its precursor is 54 amino acids long and is cut into active peptides of 32, 21 or 22, and 11 residues, all of which activate the apelin receptor; in 2019 the international pharmacology union recommended it be recognised as the receptor's second natural ligand.
It binds the receptor differently from apelin. Alanine scanning showed that elabela's C-terminal end carries the part that binds and activates the receptor, that its two cysteines are not needed, and that two acidic residues in the receptor essential for apelin do not matter for elabela. In human heart tissue it competed with apelin for binding, it switched on both G-protein and beta-arrestin pathways, and it was found in human blood vessel lining and in plasma.
In development it is needed but not always essential. Mice lacking it were sometimes lost as embryos with heart and vessel defects, at low penetrance, and developed problems in early mesoderm independently of apelin. Pregnant mice lacking it developed a preeclampsia-like syndrome with high blood pressure and protein in the urine from poor placental blood vessel growth, which infusing elabela corrected. Human embryonic stem cells make it in large amounts and need it to keep renewing themselves.
In adult animals, giving elabela acted much like apelin. In rats it increased cardiac contractility and output and widened blood vessels, and it reduced the right heart pressure and remodelling of monocrotaline-induced pulmonary hypertension, where its own expression is reduced; gene therapy delivering it had a similar effect. In mice it limited heart scarring and dysfunction after angiotensin II-induced hypertension, and two weeks of infusion after a heart attack improved heart and kidney function. A 2021 review notes that its short half-life and need for injection limit its use, and that longer-lasting versions fused to polyethylene glycol, albumin or the Fc fragment of an antibody are proposed; those are different molecules.
In people, elabela has only been measured. Plasma levels were lower in hypertensive patients than in controls, lowest in those with reduced ejection fraction, and lower levels predicted more major cardiac events over 180 days. In 335 patients, low levels separated heart failure from no heart failure with high specificity. Levels were lower in atrial fibrillation and fell with declining kidney function. The preeclampsia link seen in mice did not hold up in one study of 82 placentas and 64 women, while another found levels raised in late-onset preeclampsia. Reported concentrations differ widely between studies, from tens of picograms per millilitre in one to several nanograms per millilitre in others, a spread worth keeping in mind when comparing studies.
Elabela has never been given to people, has no approved product, and is not in any human treatment trial in the sources read.
Mechanism of Action
Elabela activates the apelin receptor, the same receptor as apelin, through a different binding mode. The two act as a pair of ligands for the receptor at different times and places in heart development.
A second key for one receptor
Its C-terminus carries the binding and activating part, and receptor residues essential for apelin are not needed for elabela.
Heart and vessel development
Embryos lacking it, in zebrafish and mice, show defects in cell movement, the heart and blood vessels.
Placenta
Secreted by the placenta, it supported placental vessel growth in mice; human data on preeclampsia conflict.
Adult heart and lungs (animals)
In rats and mice it increased contractility, widened vessels and reduced damage in models of hypertension, heart attack and pulmonary hypertension.
Published Research
Studies of elabela itself, read from their PubMed abstracts: its discovery, cell and receptor work, animal studies, and the human studies that measured it in blood. Longer-acting fusion versions are different molecules and are not carded.
Discovered as Toddler in zebrafish
Among 28 candidate signalling proteins in zebrafish embryos, the short secreted peptide Toddler was needed for mesendodermal cell movement in gastrulation; it internalised apelin receptors, and activating apelin signalling rescued toddler mutants.
Mice lacking it
Apela-null mice had low-penetrance cardiovascular defects after circulation began, vascular remodelling defects and early extraembryonic anomalies; some died of cardiac defects, independently of apelin.
Preeclampsia in mice
Elabela is secreted by the placenta; pregnant knockout mice, unlike apelin knockouts, developed preeclampsia-like proteinuria and high blood pressure from poor placental angiogenesis, which infused elabela normalised.
Stem cell self-renewal
Human embryonic stem cells secrete elabela and need it to grow and stay pluripotent; it acts through PI3K/AKT/mTORC1 signalling and an alternative cell-surface receptor, since these cells lack the apelin receptor.
Binds differently from apelin
In cells, the 32-, 22- and 11-residue fragments activated the apelin receptor; its C-terminus held the key pharmacophore, its cysteines were not needed, and receptor residues essential for apelin did not affect elabela.
An adult agonist; pulmonary hypertension
Elabela bound the apelin receptor in human heart and was present in human vessel lining and plasma; in rats ELA-32 raised contractility and cardiac output and dilated vessels, and treatment reduced right heart pressure and remodelling in monocrotaline pulmonary hypertension.
Hypertensive heart damage in mice
In mice given angiotensin II, elabela levels fell; elabela treatment prevented myocardial remodelling, fibrosis and dysfunction and reduced ferroptosis through IL-6/STAT3/GPX4 signalling.
After a heart attack in mice
Two weeks of subcutaneous apela infusion after myocardial infarction raised ejection fraction by 32% and 39% at 2 and 4 weeks and lowered urea, creatinine, NT-proBNP and urine protein against vehicle.
Gene therapy in rat pulmonary hypertension
An AAV vector delivering ELA-32 reduced right ventricular systolic pressure, NT-proBNP and pulmonary arteriole muscularisation in monocrotaline-treated rats.
No drop in preeclampsia
Placental elabela mRNA in 82 preeclamptic and 82 control pregnancies, and plasma elabela in 32 women with preterm preeclampsia against 32 controls (medians 28.5 and 20.5 pg/mL), did not differ; the authors judge the mouse link likely incorrect.
Raised in late-onset preeclampsia
In 214 pregnant women, elabela was higher in late-onset but not early-onset preeclampsia than in matched normal pregnancies, and combining it with soluble Fas improved the association.
Hypertension with heart failure
In 308 subjects, plasma elabela was lower in hypertensive patients than controls (median 4.9 against 11.8 ng/ml) and lower with reduced ejection fraction; lower levels predicted major cardiac events over 180 days (HR 0.75).
A heart failure screening marker?
In 335 patients, plasma elabela was lower in heart failure, fell with worse New York Heart Association class and ejection fraction, and distinguished heart failure with an AUC of 0.835 and specificity of 95.9%; apelin moved the opposite way.
Atrial fibrillation in hypertension
Among 162 hypertensive patients, plasma elabela was lower with atrial fibrillation (2.0 against 4.0 ng/ml) and lower still in persistent than paroxysmal fibrillation.
Atrial fibrillation and BNP
In 131 patients with arrhythmia, serum elabela was lower in atrial fibrillation than in supraventricular tachycardia and correlated inversely with BNP.
Chronic kidney disease
In 60 patients across CKD stages 1, 3 and 5 and 20 controls, serum elabela fell as kidney function fell (r 0.728 with eGFR), while apelin showed no association.
Named the second ligand
An international pharmacology union review of the apelin receptor recommends recognising Elabela/Toddler, a 54-residue precursor cleaved to 32, 21 and 11 residues, all active, as its second endogenous ligand.
Two ligands, one receptor
Apelin and Elabela share little sequence but act on the same receptor in heart development and disease, probably at different times or places, as a double ligand system.
Hypertension, kidney and pregnancy
Systemic elabela is vasodilatory, antihypertensive and protective for heart and kidney in animals, while central administration raises blood pressure; its short half-life limits use, and fused longer-acting forms are proposed.
No Established Human Dose
Elabela has never been given to people in any study we read. Its human evidence is measurement only: plasma and serum levels compared across heart failure, hypertension, atrial fibrillation, chronic kidney disease and preeclampsia, with results that conflict for preeclampsia. Every amount given in the studies on this page was given to mice, rats or cells.
What this rests on: PMID 29803833, PMID 32008387, PMID 33738301, PMID 38760403, PMID 32713238, PMID 35070372, PMID 34384364.
Educational information, not medical advice. The doses on this page come from approved labels, published studies and, where no study exists, amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
What a Buyer Needs to Know
What is sold, how it is mixed, stored and taken, and what is known about its safety, quality and legal status. Each part names its source. Where we have none, it says unknown.
What is sold
Unknown: we hold no label and no published test that says what forms or vial sizes Elabela is sold in. A vial's own label is a seller's claim, not a source.
Mixing a vial: a worked example
Unknown: no human dose of Elabela has been established (see No Established Human Dose below), so there is no amount to work out. The reconstitution calculator does the arithmetic for any vial, water and dose.
Storage before and after mixing
Unknown: no label or published stability study on file says how to store Elabela, before or after mixing. The mixing guide sets out the general rules, with their sources: keep a mixed vial in the fridge, and use it promptly, as the bacteriostatic water label says of any drug dissolved in it. The 28 days often quoted is the limit for an opened multiple-dose vial from a manufacturer, an outer limit set for sterility, not a time a mixed solution has been shown to keep. Nobody has published how long Elabela stays intact once mixed.
How it is taken
Unknown: with no established human dose, there is no established way of taking Elabela. What the human studies gave and how is set out under No Established Human Dose.
What to expect, and when
Unknown: no cited half-life and no label or trial duration on this page says how long Elabela lasts or how long it was given. Results reported in the studies are under Published Research.
Side effects, and when to stop or get help
From the Side Effects section: No human safety data; In animals, giving it into the brain raised blood pressure, the opposite of its effect in the circulation. Full list and cautions ↓
When to stop or get help: unknown; no label or trial on file sets rules for stopping Elabela. Treat a severe or unexpected reaction as a reason to stop and see a doctor.
Source: the Side Effects section below (“Elabela has not been given to people, so there are no human side-effect data”).
Interactions
Unknown: a PubMed search for human interaction studies of Elabela (reviewed 2026-10-28) found none. Unknown is not the same as safe to combine.
Every peptide's record, with its source: the interaction matrix.
Checking what you bought
Unknown: no published independent test of Elabela products is in our lab-results database yet, so how products sold under this name measure up is not known.
To read a certificate of analysis, paste it into the COA decoder; it checks the measured mass against Elabela's expected mass, 3,967.8 Da, from this entry's molecular data. Trust & Verification explains what independent testing can and cannot show.
Legal status
US: Research Chemical (Not a medicine anywhere: no approval and no human treatment trial in the sources read). Sport: Prohibited (S0 catch-all).
Country by country ↓ · Regulatory tracker
Source: this entry's approval status and the WADA Prohibited List, as in Legal Status below.
Side Effects & Contraindications
Reported Side Effects
Elabela has not been given to people, so there are no human side-effect data.
Contraindications & Cautions
Not a medicine.
Legal Status
Elabela is a research peptide with no approval anywhere in the sources read.
Frequently Asked Questions
?What is elabela?
A natural peptide hormone, also called Toddler or Apela, that activates the apelin receptor. Its active forms are 32, 21 or 22, and 11 amino acids long.
?How is elabela different from apelin?
They share almost no sequence and bind the receptor differently, but act on the same receptor. Elabela matters most in the embryo, and in adult animals its effects on the heart and vessels resembled apelin's.
?Has elabela been tested in people?
Only measured. Lower blood levels were reported in heart failure, atrial fibrillation and kidney disease; it has not been given to people.
?Is elabela linked to preeclampsia?
In mice, lacking it caused a preeclampsia-like syndrome. In women the evidence conflicts: one study found no difference, another found higher levels in late-onset preeclampsia.
References
- [pubmed] Pauli A, et al. "Toddler: an embryonic signal that promotes cell movement via Apelin receptors." Science, 2014;343(6172):1248636. PMID: 24407481.
- [pubmed] Freyer L, et al. "Loss of Apela Peptide in Mice Causes Low Penetrance Embryonic Lethality and Defects in Early Mesodermal Derivatives." Cell Rep, 2017;20(9):2116-2130. PMID: 28854362.
- [pubmed] Ho L, et al. "ELABELA deficiency promotes preeclampsia and cardiovascular malformations in mice." Science, 2017;357(6352):707-713. PMID: 28663440.
- [pubmed] Ho L, et al. "ELABELA Is an Endogenous Growth Factor that Sustains hESC Self-Renewal via the PI3K/AKT Pathway." Cell Stem Cell, 2015;17(4):435-47. PMID: 26387754.
- [pubmed] Couvineau P, et al. "Elabela/Toddler and apelin bind differently to the apelin receptor." FASEB J, 2020;34(6):7989-8000. PMID: 32301550.
- [pubmed] Yang P, et al. "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." Circulation, 2017;135(12):1160-1173. PMID: 28137936.
- [pubmed] Zhang Z, et al. "Elabela alleviates ferroptosis, myocardial remodeling, fibrosis and heart dysfunction in hypertensive mice by modulating the IL-6/STAT3/GPX4 signaling." Free Radic Biol Med, 2022;181:130-142. PMID: 35122997.
- [pubmed] Pan Y, et al. "Apela improves cardiac and renal function in mice with acute myocardial infarction." J Cell Mol Med, 2020;24(18):10382-10390. PMID: 32686917.
- [pubmed] Hu Y, et al. "Apela gene therapy alleviates pulmonary hypertension in rats." FASEB J, 2022;36(7):e22431. PMID: 35747913.
- [pubmed] Pritchard N, et al. "ELABELA/APELA Levels Are Not Decreased in the Maternal Circulation or Placenta among Women with Preeclampsia." Am J Pathol, 2018;188(8):1749-1753. PMID: 29803833.
- [pubmed] Para R, et al. "Maternal circulating concentrations of soluble Fas and Elabela in early- and late-onset preeclampsia." J Matern Fetal Neonatal Med, 2022;35(2):316-329. PMID: 32008387.
- [pubmed] Ma Z, et al. "Lower Plasma Elabela Levels in Hypertensive Patients With Heart Failure Predict the Occurrence of Major Adverse Cardiac Events: A Preliminary Study." Front Cardiovasc Med, 2021;8:638468. PMID: 33738301.
- [pubmed] Liu C, et al. "Decreased plasma ELABELA level as a novel screening indicator for heart failure: a cohort and observational study." Sci Rep, 2024;14(1):11333. PMID: 38760403.
- [pubmed] Ma Z, et al. "Declined ELABELA plasma levels in hypertension patients with atrial fibrillation: a case control study." BMC Cardiovasc Disord, 2021;21(1):390. PMID: 34384364.
- [pubmed] Cui C, et al. "ELABELA acts as a protective biomarker in patients with atrial fibrillation." J Thorac Dis, 2021;13(12):6876-6884. PMID: 35070372.
- [pubmed] Lu X, et al. "Serum elabela and apelin levels during different stages of chronic kidney disease." Ren Fail, 2020;42(1):667-672. PMID: 32713238.
- [review] Read C, et al. "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." Pharmacol Rev, 2019;71(4):467-502. PMID: 31492821.
- [review] Kuba K, et al. "Apelin and Elabela/Toddler; double ligands for APJ/Apelin receptor in heart development, physiology, and pathology." Peptides, 2019;111:62-70. PMID: 29684595.
- [review] Xu C. "The Elabela in hypertension, cardiovascular disease, renal disease, and preeclampsia: an update." J Hypertens, 2021;39(1):12-22. PMID: 32740407.
- [other] UniProt P0DMC3 (ELA_HUMAN), chain residues 23-54, apelin receptor early endogenous ligand; read October 28, 2026. https://www.uniprot.org/uniprotkb/P0DMC3/entry
Sources & Citations
Studies were read from their PubMed abstracts on October 28, 2026; the sequence is from UniProt P0DMC3. Elabela has no label.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.