Apelin

Summary

Apelin is an endogenous peptide hormone and the cognate ligand of the APJ (APLNR) receptor. It exists in multiple isoforms (apelin-13, apelin-17, apelin-36 being most studied). It plays key roles in cardiovascular regulation, fluid homeostasis, and energy metabolism. Reduced apelin signaling is associated with heart failure, pulmonary arterial hypertension (PAH), and diabetes. Multiple synthetic apelin analogs and biased agonists are under clinical investigation, particularly for heart failure and PAH.

Mechanism of Action

Endogenous ligand of the APJ receptor (APLNR), a G protein-coupled receptor. Activates Gi signaling to reduce cAMP, activates β-arrestin pathways, and modulates PI3K/Akt signaling. Produces positive inotropy, vasodilation via nitric oxide release, and inhibits ADH/vasopressin release. Exerts cardioprotective and anti-fibrotic effects.

Routes of Administration

Goals & Uses

• Heart failure treatmentCardiovascularModerate
• Metabolic syndrome / obesityMetabolicLow
• Cardioprotection / ischemia-reperfusion injuryCardiovascularLow
• Fluid balance / hyponatremiaEndocrine / RenalLow
• Pulmonary arterial hypertension (PAH)Cardiovascular / PulmonaryModerate

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

Drug Interactions

• ACE2 inhibitors / substratesLow
• 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
• Pediatric populationsAgeRelative

Regulatory Status

• European UnionInvestigationalResearch-stage; some analog trials conducted in EU (e.g., MM07 for PAH in UK/EU institutions).
• United StatesInvestigationalNo FDA-approved apelin product. Analogs (e.g., BL-1249 analog series) in early clinical trials for PAH and heart failure.
• United KingdomInvestigationalUniversity of Edinburgh and collaborators have conducted Phase I/II trials with apelin-13 and analogs in heart failure and PAH.

No approved therapeutic apelin product exists in any major jurisdiction as of 2024. Research-grade apelin peptides are used in laboratory and early clinical settings. Analogs (e.g., MM07, CMF-019) are in Phase I/II trials for heart failure and PAH.

Evidence & Sources

No sources recorded yet.