Apelin
Also known as: [Pyr1]apelin-13, apelin-13, apelin-17, apelin-36, Apelin‑13, Apelin‑36, APJ ligand, APLN, ELABELA
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Summary
Apelin is an endogenous neuropeptide that binds the apelin (APJ) receptor and influences cardiovascular, renal and metabolic physiology. It is released from endothelial cells, heart, kidney and skeletal muscle, especially during exercise. Research highlights its vasodilatory, inotropic, anti‑inflammatory, anti‑fibrotic and muscle‑protective actions, positioning it as a candidate therapeutic target for heart failure, hypertension, kidney disease, obesity, type‑2 diabetes and age‑related sarcopenia.
Mechanism of Action
Apelin activates the G‑protein‑coupled apelin receptor (APLNR), stimulating downstream pathways that increase nitric‑oxide production in endothelial cells, promote cardiac contractility, and lower systemic vascular resistance. In skeletal muscle, apelin signaling drives mitochondrial biogenesis, autophagy and anti‑inflammatory cascades, enhancing muscle stem‑cell activity. Renally, it promotes diuresis via direct tubular effects and central mechanisms. These actions collectively oppose renin‑angiotensin and vasopressin systems.
What the Research Shows
A 2023 review described apelin’s capacity to induce endothelium‑dependent vasodilation, inotropy, blood‑pressure reduction, angiogenesis, anti‑arrhythmic, anti‑thrombotic, anti‑inflammatory and anti‑fibrotic effects, suggesting broad therapeutic promise for cardiovascular, renal and metabolic disorders. A 2024 myokine review highlighted exercise‑induced muscle secretion of apelin that influences bone remodeling. Pre‑clinical work (Nat Med 2018) showed age‑related declines in apelin, and that restoring its signaling in mice improved muscle strength via mitochondrial and autophagic pathways, indicating potential for sarcopenia treatment. A sarcopenia drug review listed apelin among emerging candidates, though human trials are pending. Conversely, a 2022 meta‑analysis of exercise trials in type‑2 diabetes found no consistent change in circulating apelin levels with training.
Reported Benefits
Animal studies demonstrate that apelin can lower blood pressure, enhance cardiac output, promote new blood‑vessel formation and reduce cardiac fibrosis. In muscle, apelin improves mitochondrial function, stimulates autophagy, reduces inflammation and supports regeneration of muscle stem cells, leading to better strength in aged rodents. These multi‑system actions underpin its investigation as a therapeutic lead for heart failure, hypertension, kidney disease, metabolic syndrome and age‑related muscle loss.
Limitations of the Evidence
Human evidence is limited to observational and pre‑clinical data; no approved apelin‑based medicines exist. Clinical trials in sarcopenia are still early, and exercise studies have not shown reliable increases in circulating apelin. Safety, optimal dosing, and long‑term effects remain undefined, necessitating rigorous randomized trials before therapeutic use can be confirmed.
Safety Considerations
The abstracts do not report adverse events from apelin administration, reflecting the early stage of research. Potential risks may include excessive vasodilation leading to hypotension or unwanted cardiac stimulation. Until human safety data are available, caution is warranted, and apelin should be considered investigational only.
How It Is Administered
Investigational apelin formulations have been administered intravenously or subcutaneously in pre‑clinical studies. Peptide analogs are being explored for stability, but no commercial product is available.
Routes of Administration
Goals & Uses
- Heart failureCardiovascularModerate
- Heart failure treatmentCardiovascularModerate
- Metabolic syndrome / obesityMetabolicLow
- Cardioprotection / ischemia-reperfusion injuryCardiovascularLow
- Fluid balance / hyponatremiaEndocrine / RenalLow
- Pulmonary arterial hypertension (PAH)Cardiovascular / PulmonaryModerate
- Pulmonary arterial hypertensionCardiovascular / PulmonaryModerate
- Type 2 diabetes mellitusMetabolicLow
Contraindications
- PregnancyPopulationModeratePotential fetal risk or insufficient safety data
- Known hypersensitivity to apelin or formulation componentsImmunologicHigh
- Severe hypotensionCardiovascularHigh
Adverse Effects
- Injection site reactionsLocalUncommon
- HypotensionCardiovascularCommonLow blood pressure
- FlushingVascularUncommonWarmth and redness of the skin
- TachycardiaCardiovascularUncommonAbnormally fast heart rate
- NauseaGastrointestinalRareFeeling of sickness or urge to vomit
Drug Interactions
- Beta‑blockersLow
- ACE2 inhibitors / substratesLow
- ACE inhibitorsModerate
- AntihypertensivesModerateMay potentiate hypotensive effects in some contexts
- Vasopressin / AVP analogues (e.g., desmopressin)Moderate
Population Constraints
- PregnancyReproductive SafetyRelative
- Elderly with hemodynamic instabilityAge / CardiovascularRelative
- Renal impairmentOrgan ImpairmentRelative
- Severe renal impairmentOrgan ImpairmentRelative
- Pediatric populationsAgeRelative
- Pregnant womenReproductiveRelative
Regulatory Status
- European UnionUnapprovedNo marketing authorization; clinical research ongoing
- United StatesUnapprovedInvestigational New Drug (IND) status for early‑phase trials
- United KingdomInvestigationalUniversity of Edinburgh and collaborators have conducted Phase I/II trials with apelin-13 and analogs in heart failure and PAH.
No approved pharmaceutical product containing apelin; investigational use only in early‑phase clinical trials.
Evidence & Sources
- Journal ArticleModerateChapman FA, et al.2023-01-01T00:00:00.000000Z
- Journal ArticleModerateZhao Z, et al.2023-01-01T00:00:00.000000Z
- Journal ArticleModerateRolland Y, et al.2023-01-01T00:00:00.000000Z
- Journal ArticleModerateChen ZT, et al.2024-01-01T00:00:00.000000Z
- Journal ArticleModerateVinel C, et al.2018-01-01T00:00:00.000000Z
- Journal ArticleHighGarcía-Hermoso A, et al.2023-01-01T00:00:00.000000Z
Frequently Asked Questions
What is apelin and where is it produced?
Apelin is an endogenous peptide that binds the APJ (apelin) receptor. It is secreted by endothelial cells, the heart, kidneys and skeletal muscle, and its release increases during physical activity.
Can apelin be used to treat heart failure or high blood pressure?
Pre‑clinical and review data suggest apelin can improve heart contractility, cause vasodilation and lower blood pressure, but no human trials have yet demonstrated efficacy or safety for these indications.
Is apelin effective for preventing age‑related muscle loss?
In mouse models, restoring apelin signaling reversed sarcopenia by enhancing mitochondrial function, autophagy and muscle‑stem‑cell activity. Human studies are still pending, so its clinical benefit remains unproven.
Does exercise increase apelin levels in people with type‑2 diabetes?
A systematic review of randomized trials found no significant change in circulating apelin after exercise training in type‑2 diabetes patients.
Are there any known side effects of apelin therapy?
Safety data are limited; theoretical concerns include excessive vasodilation and hypotension. Formal safety assessments in humans have not yet been reported.
What is Apelin used for?
Apelin is educationally associated with: Heart failure, Heart failure treatment, Metabolic syndrome / obesity, Cardioprotection / ischemia-reperfusion injury, Fluid balance / hyponatremia, Pulmonary arterial hypertension (PAH), Pulmonary arterial hypertension, Type 2 diabetes mellitus. Educational only — not medical advice.
How is Apelin administered?
Recorded routes of administration: Intranasal, Intravenous, Subcutaneous.
What are the potential side effects of Apelin?
Reported adverse effects include: Injection site reactions, Hypotension, Flushing, Tachycardia, Nausea. This list is not exhaustive — consult a qualified clinician.
Who should avoid Apelin?
Recorded contraindications: Pregnancy, Known hypersensitivity to apelin or formulation components, Severe hypotension. Consult a qualified clinician before use.