Apelin-13
Also known as: [Pyr1]apelin-13, pyroglutamyl apelin-13, apelin-13 peptide, APLN-13, pGlu-apelin-13
Endogenous peptide — APJ receptor agonist; adipokine/vasoactive peptide; cardiovascular and neuroendocrine regulator
What it is
Apelin-13 is a naturally occurring peptide your body makes, best known for keeping blood pressure in check and helping the heart pump more effectively. Researchers are studying it for conditions like pulmonary arterial hypertension, heart failure, stroke recovery, and metabolic disorders. It is not approved as a drug, but clinical investigation is active.
The scientific side
apelin-13 is a 13-amino-acid peptide and the most biologically active isoform of the apelin family, encoded by the APLN gene. It exerts its effects primarily through binding and activating the APJ receptor (also termed APLNR), a Gi/Go-coupled seven-transmembrane G-protein-coupled receptor expressed widely in the cardiovascular system, brain, lung, kidney, and adipose tissue. Upon APJ activation, apelin-13 triggers downstream signaling through multiple pathways including PI3K/Akt, MAPK/ERK, and eNOS, producing context-dependent effects in target tissues. In the cardiovascular system, apelin-13 produces positive inotropy — increasing cardiac contractility — while simultaneously causing vasodilation through endothelial nitric oxide synthase (eNOS) activation and nitric oxide (NO) production. This combination lowers systemic vascular resistance while maintaining or increasing cardiac output, explaining its attractiveness as a heart failure and pulmonary arterial hypertension (PAH) target. In PAH, the apelin/APJ signaling axis is downregulated; reduced circulating apelin correlates with disease severity. Restoration of apelin-APJ signaling attenuates pulmonary vascular remodeling by upregulating Krüppel-like factor 2 (KLF2), promoting eNOS expression, and suppressing pathological smooth muscle proliferation. Apelin-13 also exerts anti-diuretic hormone (ADH/AVP) antagonism: it counteracts vasopressin-induced water retention, promoting aquaresis without natriuresis, a mechanism explored for hyponatremia correction. In the renin-angiotensin system (RAS), apelin-13 acts as a functional counterregulator, suppressing renin production and reducing circulating angiotensin II, partially through cAMP-dependent inhibition of (pro)renin receptor signaling. Neuroprotective mechanisms include inhibition of NLRP3 inflammasome-mediated pyroptosis, suppression of apoptosis and oxidative stress via Nrf2/HO-1 activation, attenuation of neuroinflammation, and promotion of angiogenesis after ischemic injury. In metabolic contexts, apelin-13 enhances insulin sensitivity, promotes glucose uptake, and modulates energy metabolism in adipose and skeletal muscle tissue. The pyroglutamylated form [Pyr1]apelin-13 is more resistant to proteolytic degradation and retains full APJ agonist activity, making it the preferred form in clinical infusion studies.
Class: Endogenous peptide — APJ receptor agonist; adipokine/vasoactive peptide; cardiovascular and neuroendocrine regulator
Administration & storage
- Administration
- Intravenous infusion — used in clinical trial NCT06277336 ([Pyr1]apelin-13 in SIAD) and NCT01457170 (hemodynamic studies)Intravenous bolus — used in rat cardiac suppression reversal model (PMID: 38583586)Intracerebroventricular (ICV) injection — used in rat fear extinction and neuroprotection models (PMID: 31513835)Local delivery via nanoparticle (PLGA/macrophage-membrane system) for brain targeting (PMID: 39263632)Local delivery via ROS-responsive hydrogel for spinal cord injury application (PMID: 39794784)
- Storage
- Research-grade apelin-13 lyophilized powder: store at -20°C or below. Reconstituted solutions: -80°C, single-use aliquots recommended. Avoid repeated freeze-thaw cycles. [Pyr1]apelin-13 is more stable than unmodified apelin-13 due to cyclized N-terminus reducing aminopeptidase susceptibility.
- Cautions
- No approved clinical safety profile exists for apelin-13 as a drug. All safety observations derive from investigational studies and preclinical data.,Hypotensive effects: Apelin-13 is a potent vasodilator. IV administration in human studies (NCT01457170, NCT06277336) carries risk of clinically significant hypotension, particularly in patients with pre-existing low blood pressure or dehydration.,Cardiac effects: Positive inotropy combined with vasodilation can precipitate arrhythmia or hemodynamic instability in susceptible patients, including those with structural heart disease.,Short plasma half-life: Unmodified apelin-13 is rapidly degraded by plasma angiotensin-converting enzyme 2 (ACE2) and aminopeptidase P, with a half-life of minutes. This means effects are short-lived but also limits dosing windows; [Pyr1]apelin-13 has a longer half-life but is still short-acting.,Endogenous system perturbation: Pharmacological doses of apelin-13 may dysregulate endogenous apelin/APJ tone, RAS counterregulation, and fluid balance in ways not yet fully characterized in humans.,No long-term safety data: No chronic administration safety data exist in humans. All human data are from acute infusion studies of hours to days duration.
Legal & regulatory status
Not FDA-approved as a drug. Apelin-13 and related apelin isoforms are investigational compounds. No approved product based on apelin-13 exists in the United States as of 2026. BMS-986224 (Bristol-Myers Squibb), an oral…
Apelin-13 is an endogenous peptide that acts as a positive inotrope and vasodilator. It does not appear by name on the WADA Prohibited List as of the 2024 edition. However, peptides that activate the APJ receptor and…
Not approved in Canada as a therapeutic drug. Apelin-13 is available as a research-grade peptide reagent but holds no Health Canada drug identification number (DIN). Investigational clinical work involving apelin…
What it's studied for
- Pulmonary arterial hypertension (PAH) — vasodilation and vascular remodeling attenuation Preclinical + Early Clinical (Phase I/IIa)
- Heart failure — positive inotropy and afterload reduction Preclinical + Early Clinical
- Hyponatremia and fluid homeostasis — anti-ADH/aquaretic effects Phase I Clinical (completed)
- Neuroprotection and neurological injury — stroke, traumatic brain injury, spinal cord injury Preclinical
- Metabolic disease — obesity, insulin resistance, type 2 diabetes Preclinical + Observational Human
- Bone and musculoskeletal protection — osteoporosis, arthritis, periprosthetic osteolysis Preclinical
- Thromboembolic risk — biomarker in deep vein thrombosis and pulmonary embolism Observational / Biomarker
- Critical illness prognosis — biomarker in ICU patients Observational Clinical
Safety signals
- Acute hypotension from vasodilatory mechanism
- Rapid plasma degradation limiting dose predictability (ACE2 and aminopeptidase P cleavage)
- Arrhythmia risk from positive inotropy in structurally abnormal hearts
- Fluid balance and electrolyte perturbation — aquaretic and anti-ADH effects
- Unknown chronic safety profile — no long-term human data
- Biphasic blood pressure effects — central pressor vs. peripheral vasodilatory actions
- Potential pro-coagulant / thrombosis signal at elevated concentrations
Contraindications
About these dose ranges
Dose ranges below reflect commonly reported community protocols. Where published research cites a specific dose, the PMID is linked. Doses without citations are not clinical recommendations — they reflect what practitioners and researchers commonly report using.
Community-reported dosing
| Route | Dose | Frequency / Duration | Population / context | Source tier |
|---|---|---|---|---|
| Unspecified | [Pyr1]apelin-13 intravenous infusion — dose not publicly specified in registry (NCT06277336) | — | Healthy volunteers — induced SIAD (hyponatremia) model, intravenous administration | Research |
| Unspecified | Typically 10–100 nmol/kg IV or intracerebroventricularly (ICV) in rodent studies | — | Preclinical — rat cardiovascular and hypertension models | Research |
| Unspecified | Encapsulated in PLGA nanoparticles (MM/ANPs) or ROS-responsive hydrogels; local tissue delivery | — | Preclinical — nanoparticle and hydrogel drug delivery systems (stroke, SCI) | Research |
| Intravenous infusion (human studies); ICV or intranasal (preclinical) | Not established — IV infusion doses used under clinical trial IND conditions only; preclinical rodent range 10–100 nmol/kg | Acute single-session infusions in human research settings | Healthy volunteers and investigational clinical trial populations |