Apelin

Also known as: APJ endogenous ligand, APLN, Q9ULZ1

**Mechanism of Action** Apelin, encoded by the *APLN* gene (UniProt Q9ULZ1), is an endogenous peptide hormone that acts as the primary ligand for the G protein-coupled apelin receptor (APJ). Binding to APJ activates multiple intracellular signaling cascades, including Gαi/o-mediated inhibition of cAMP production, β-arrestin recruitment, and downstream phosphorylation of ERK1/2 and Akt pathways. These signals modulate vascular tone, cardiac contractility, and fluid homeostasis, primarily through nitric oxide-dependent vasodilation and regulation of aquaporin expression in the kidney. **Key Research Findings** Preclinical studies demonstrate apelin’s potent positive inotropic effects in isolated cardiomyocytes and intact hearts, with improved cardiac output in models of heart failure. Apelin also reduces mean arterial pressure via endothelial nitric oxide synthase activation and enhances diuresis by antagonizing vasopressin. In metabolic studies, apelin improves insulin sensitivity and glucose uptake in skeletal muscle. However, its short plasma half-life (~5 minutes) limits translational utility, prompting development of stable analogs. Over 2,941 PubMed-indexed studies support its role in cardiovascular, metabolic, and fluid-regulatory systems. **Clinical Relevance** Apelin is under experimental investigation for heart failure, hypertension, and metabolic disorders. Phase I/II trials of long-acting apelin analogs (e.g., BMS-986224) show dose-dependent hemodynamic effects, including reduced afterload and increased cardiac index, with favorable safety profiles. No approved therapies currently exist, and further studies are needed to establish efficacy in chronic disease settings. For research purposes only — not medical advice.

Key data

Mechanism of action

Peptide hormone that functions as endogenous ligand for the G protein-coupled apelin receptor (APLNR/APJ), that plays a role in cadiovascular homeostasis (PubMed:10525157, PubMed:22810587, PubMed:35817871, PubMed:38428423). Functions as a balanced agonist activating both G(i) protein pathway and beta-arrestin pathway of APLNR (PubMed:22810587, PubMed:38428423). Downstream G proteins activation, apelin can inhibit cAMP production and activate key intracellular effectors such as ERKs (PubMed:22810587, PubMed:35817871, PubMed:38428423). On the other hand, APLNR activation induces beta-arrestin recruitment to the membrane leading to desensitization and internalization of the receptor (PubMed:22810587, PubMed:38428423). Apelin blunts cardiac hypertrophic induction from APLNR on response to pathological stimuli, but also induces myocardial hypertrophy under normal conditions (PubMed:22810587, PubMed:38428423). Apelin-36 dissociates more hardly than (pyroglu)apelin-13 from APLNR (By similarity). Involved in the regulation of cardiac precursor cell movements during gastrulation and heart morphogenesis (By similarity). Has an inhibitory effect on cytokine production in response to T-cell receptor/CD3 cross-linking; the oral intake of apelin in the colostrum and the milk might therefore modulate immune responses in neonates (By similarity). Plays a role in early coronary blood vessels formation (By similarity). Mediates myocardial contractility in an ERK1/2-dependent manner (By similarity). May also have a role in the central control of body fluid homeostasis by influencing vasopressin release and drinking behavior (By similarity)

Research & studies

Frequently asked questions

Related peptides