Apelin Signaling in Cardiovascular and Metabolic Health

The apelinergic system encompasses the G protein–coupled APJ receptor and its endogenous ligands, apelin and Elabela. It exerts potent cardiovascular actions including endothelium-dependent vasodilatation, positive inotropy, angiogenesis and blood-pressure regulation. Concurrently, apelin modulates fluid homeostasis and renal perfusion, opposing the renin–angiotensin axis and promoting natriuresis. Its metabolic functions extend to glucose and lipid metabolism, insulin secretion and adipose tissue regulation, positioning apelin as a mediator of energy balance. Dysregulation of apelin signalling features in pathologies such as heart failure, pulmonary arterial hypertension, chronic kidney disease, obesity and type 2 diabetes. Accumulating evidence highlights anti-inflammatory and anti-fibrotic roles, as well as protective effects against arrhythmia and thrombosis. Therapeutic strategies under investigation span receptor agonists, biased ligands and long-acting analogues, alongside the development of diagnostic tracers to visualise APJ expression in vivo. The global burden of cardiovascular and metabolic disorders underscores the translational potential of apelin-based interventions for personalised management of multifactorial disease states.

Research from Nature Portfolio

In clinical translational research, infusion of pyroglutamated apelin-13 in patients with chronic kidney disease and matched healthy volunteers reduced mean arterial pressure, decreased systemic vascular resistance and enhanced cardiac index in a dose-dependent manner while augmenting renal blood flow and natriuresis. In kidney disease cohorts, short-term administration also lowered proteinuria and modulated glomerular filtration parameters, supporting the rationale for long-acting oral apelin receptor agonists in conditions of disrupted salt and water balance. At the mechanistic level, genetic labelling of sprouting endothelial cells via APJ promoter activity revealed reactivation of apelin gene expression in ischaemic and tumour angiogenesis models, enabling selective targeting of neovessels without affecting quiescent vasculature. This approach demonstrated that disruption of APJ-driven sprouting attenuates pathological vascularisation, offering a precision tool for vascular therapy and a blueprint for targeted modulation of disease-driven angiogenesis.

Apelin Signaling in Cardiovascular and Metabolic Health publication trend

The graph below shows the total number of articles in apelin signaling in cardiovascular and metabolic health across all publications each year (not limited to Nature Index journals).

Technical terms

Apelin: Endogenous peptide ligand of the APJ receptor that regulates cardiovascular, renal and metabolic processes.

APJ receptor: G protein–coupled receptor (also known as APLNR) through which apelin and Elabela mediate physiological effects.

Elabela (Toddler): Second endogenous APJ receptor ligand with roles in embryonic development and adult cardiovascular function.

Vasodilatation: Relaxation of blood vessel smooth muscle leading to increased vessel diameter and reduced vascular resistance.

Inotropy: Modulation of cardiac muscle contractility, influencing the force of heart contractions.

References

1. Cardiovascular and renal effects of apelin in chronic kidney disease: a randomised, double-blind, placebo-controlled, crossover study. Nature Communications (2024).
2. Targeting the apelin system for the treatment of cardiovascular diseases. Cardiovascular Research (2023).
3. Design and preclinical evaluation of a novel apelin-based PET radiotracer targeting APJ receptor for molecular imaging of angiogenesis. Angiogenesis (2023).
4. Genetic targeting of sprouting angiogenesis using Apln-CreER. Nature Communications (2015).
5. Apelin and energy metabolism. Frontiers in Physiology (2015).
6. Apelin, Elabela/Toddler, and biased agonists as novel therapeutic agents in the cardiovascular system. Trends in Pharmacological Sciences (2015).