Apelin

APLN gene product; isoforms apelin-36, apelin-17, apelin-13 and pyroglutamyl-apelin-13 (the dominant circulating form); receptor APJ / APLNR. ELABELA (Toddler) is a second, separate ligand of the same receptor

Cardiovascular & circulation

Awaiting medical reviewEN ES DE FR PT ZH+ Follow for updates

Summary

Class: Naturally occurring peptide hormone; a 77-amino-acid precursor cleaved into active fragments of 36, 17 and 13 amino acids
Mechanism: Activates the APJ receptor to increase heart contractility without raising oxygen cost much, widen blood vessels via nitric oxide, and oppose the angiotensin II arm of the renin–angiotensin system
Routes studied: Intravenous and intra-arterial infusion in human physiology studies; no chronic human dosing of any kind
Half-life: Minutes. Apelin is rapidly degraded by ACE2 and neprilysin, which is the central obstacle to using it as a drug
Storage: Research peptide; lyophilised, frozen for long-term storage. Not a consumer product
Regulatory status: Not approved anywhere. No apelin or APJ agonist product is licensed as of this review

Doses are as reported in studies or by the community — never recommendations.

1What it is

Apelin is one of your own signalling peptides, identified in 1998 as the natural partner for an orphan receptor called APJ that had been sitting unexplained in the genome. It is made by the cells lining blood vessels, by fat tissue (it is counted among the adipokines), by the heart, lung and mammary gland, and in the brain.

Its natural job is a mix of circulatory and metabolic housekeeping: it supports heart contraction, keeps vessels relaxed, participates in fluid balance alongside vasopressin, and improves how tissues handle glucose. It is also the counterweight to angiotensin II — and in a neat biological twist, the enzyme ACE2 that generates angiotensin-(1-7) (#153) is the same enzyme that chews up apelin. Interest in it is almost entirely academic and pharmaceutical. Community use: essentially none documented, and the very short means injected apelin would do little even if someone tried.

2How it's thought to work

Heart. activates APJ on cardiomyocytes, increasing contractility through a pathway that does not depend on raising intracellular calcium the way adrenergic drugs do — so it is described as an "energy-efficient" inotrope.

Vessels. triggers nitric-oxide-dependent dilation in intact endothelium (the effect flips to constriction if the endothelium is stripped, which is why the literature looks contradictory at first glance).

RAS balance. opposes angiotensin II's vasoconstriction and pro-fibrotic signalling; APJ and the angiotensin receptor interact directly.

Metabolism. improves insulin sensitivity and glucose uptake in muscle and fat in animal models; apelin rises with obesity, which may be compensatory.

Fluid balance. acts in the hypothalamus with an effect opposite to vasopressin on water handling.

Mechanical stretch. ELABELA/apelin–APJ signalling is also mechanosensitive, which links the pathway to cardiac loading.

Apelin at the APJ receptor. Two answers come from one receptor: the vessel widens, and the heart muscle contracts more forcefully — an inotropic effect that does not run through the adrenergic system.Schematic — not to scale

3What the research shows

Human haemodynamics in healthy volunteers

Intra-arterial apelin produced dose-dependent forearm vasodilation; systemic infusion increased cardiac output and lowered peripheral resistance without a rise in heart rate, in small, carefully instrumented studies from the Edinburgh group (Japp 2008, Circulation). [2]

Human haemodynamics in heart failure

In patients with chronic heart failure, pyr-apelin-13 infusion raised cardiac index and lowered pulmonary and systemic vascular resistance acutely (Japp 2010, J Am Coll Cardiol; Barnes 2013, Heart). These are the strongest human data on apelin and they cover hours, not weeks. [3][4]

Circulating apelin as a biomarker

Apelin levels are altered in heart failure, pulmonary arterial hypertension, obesity and pre-eclampsia, but the direction varies by stage and assay, and no apelin assay is in routine clinical use.

Cardiac remodelling, fibrosis, pulmonary hypertension

Animal models consistently report that apelin or APJ agonism reduces hypertrophy and fibrosis, improves survival after infarction, and attenuates pulmonary hypertension. ELABELA shows a similar profile. All rodent.

Metabolic effects

Rodent studies report improved insulin sensitivity, increased glucose uptake and effects on food intake. No human metabolic trial.

Graded D/B

Drug development

Because the peptide is degraded in minutes, work has shifted to stabilised analogues and small-molecule APJ (for example the compound series including CMF-019) and to biased agonists intended to keep the inotropic effect without receptor desensitisation. None has an established human efficacy result; check registries for current programmes †.

4Reported side effects and interactions

Literature-reported

Short infusions in volunteers and heart-failure patients were well tolerated. Expected effects are a fall in blood pressure and flushing at higher infusion rates. No chronic human safety data exist at all.

Community-reported

None. Not in self-directed use.

Theoretical. A positive inotrope plus vasodilator is a combination that has historically looked good acutely and harmful chronically in heart failure (the lesson of milrinone and similar agents), so chronic APJ agonism cannot be assumed safe from acute data. Apelin also promotes and is expressed in tumours.

Interactions. Additive hypotension with vasodilators and antihypertensives. ACE2 activity governs apelin breakdown, so anything altering ACE2 could in principle alter apelin exposure — unstudied in humans.

Markers researchers commonly monitor

In human studies these are the measures that matter; there is no home-monitoring context for this compound.

Marker	Why it's watched
Blood pressure and heart rate	the dose-limiting effects are hypotension and flushing.
Cardiac index / cardiac output	the primary pharmacodynamic endpoint in the heart-failure infusion studies, measured invasively or by echo.
Systemic and pulmonary vascular resistance	where the vasodilator effect shows up.
NT-proBNP	standard heart-failure context marker, used to characterise the population rather than to track apelin effect.
Fasting glucose and insulin sensitivity measures	relevant to the metabolic hypothesis, which remains animal-level.
Urine output and plasma sodium	the pathway interacts with vasopressin and water handling.

Free for everyone. Safety information is never behind a paywall.

5Reconstitution and handling

Not applicable as a consumer practice. Apelin-13 and pyr-apelin-13 are supplied as research-grade peptides for laboratory and clinical-research use, prepared and infused under monitoring. Pyr-apelin-13 is used in human studies specifically because the pyroglutamyl modification resists aminopeptidase cleavage; plain apelin-13 degrades even faster. No calculator preset applies.

6Commonly studied alongside

Angiotensin-(1-7) (#153 — the other counter-regulatory RAS peptide, sharing ACE2), adrenomedullin (#151), urocortin 2 (#155), natriuretic peptides. ELABELA is studied as the alternative endogenous APJ ligand rather than as a separate compound.

Informational cross-links. Not stack recommendations.

7Regulatory status by region

Region	Status (checked —)
United States	Not FDA-approved; research use only
European Union	Not authorised
United Kingdom	Not licensed
Australia	Not approved
South Africa	Not registered
Sport	Not specifically listed by WADA; a peptide hormone acting on the cardiovascular system would likely be captured by S0 (non-approved substances) if used. Check the current list

8Open questions

Can APJ agonism be sustained without receptor desensitisation and without the chronic harm seen with other inotropes?
Does any metabolic benefit seen in rodents appear in humans?
What do raised endogenous apelin levels in obesity and heart failure actually mean — compensation, or contribution?
Is ELABELA the more tractable therapeutic ligand?

9References

1Tatemoto K et al. (1998). Isolation and characterization of a novel endogenous peptide ligand for the human APJ receptor. Biochem Biophys Res Commun. PubMed · DOI
2Japp AG et al. (2008). Vascular effects of apelin in vivo in man. Circulation. PubMed · DOI
3Japp AG et al. (2010). Acute cardiovascular effects of apelin in humans: potential role in patients with chronic heart failure. J Am Coll Cardiol. PubMed · DOI
4Barnes GD et al. (2013). Sustained cardiovascular actions of APJ agonism during renin–angiotensin system activation and in patients with heart failure. Heart [verify journal]. PubMed · DOI
5Chun HJ et al. (2008). Apelin signaling antagonizes Ang II effects in mouse models of atherosclerosis. J Clin Invest. PubMed · DOI
6Chng SC, Ho L, Tian J, Reversade B (2013). ELABELA: a hormone essential for heart development signals via the apelin receptor. Dev Cell. PubMed · DOI
7Yang P et al. (2017). Elabela/Toddler is an endogenous agonist of the apelin APJ receptor in the adult cardiovascular system. Circulation [verify]. PubMed

References are being resolved to PubMed/DOI identifiers; links search PubMed for the citation until then.

† Being confirmed by our reviewers against current sources.

10Community

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Self-reported side effects Phase 2

Not enough data yet. 0 of the 50 members needed have logged this compound for 4+ weeks. We don't show anything below 50, so no one can be identified.

11Page history

30 Oct 2026Profile published — awaiting medical review

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