The apelin receptor is a potential target in the treatment of heart failure and pulmonary arterial hypertension where levels of endogenous apelin peptides are reduced but significant receptor levels remain.
In this study, we determined how post-infarct heart failure (HF) and a high fat diet (HFD) affect expression of the apelin APJ receptor (APJR) and the V1a (V1aR) and V1b (V1bR) vasopressin receptors in the hypothalamus, the heart, and the retroperitoneal adipose tissue.
The APJ receptor and its endogenous peptidic ligand apelin have been implicated as important modulators of cardiovascular function, and APJ receptor agonists may be beneficial in the treatment of heart failure.
Indeed, ongoing studies are investigating the potential benefits of apelin and apelin-mimetics for disorders such as heart failure and pulmonary arterial hypertension.
At a cutoff lower than 126 ng/l, the sensitivity of serum apelin to predict unfavorable prognosis in children with HF was 96% with a specificity of 82%.
These findings underscore apelin's unique potential as a therapeutic agent that can simultaneously support cardiac function and protect against the hypertrophy-heart failure transition.
Based on these favorable hemodynamic effects, apelin and apelin-like analogs are being developed for treating heart failure and related disorders; however, the molecular mechanisms underlying apelin-induced coronary vasodilation are unknown.
This may have potential clinical applications as apelin has been introduced as a potential therapeutic agent in heart failure and opioids are being currently used in the treatment of myocardial infarction.
In summary, these new compounds, which favor diuresis and improve cardiac contractility while reducing vascular resistances, represent promising candidates for the treatment of heart failure and water retention/hyponatremic disorders.-Gerbier, R., Alvear-Perez, R., Margathe, J.-F., Flahault, A., Couvineau, P., Gao, J., De Mota, N., Dabire, H., Li, B., Ceraudo, E., Hus-Citharel, A., Esteoulle, L., Bisoo, C., Hibert, M., Berdeaux, A., Iturrioz, X., Bonnet, D., Llorens-Cortes, C. Development of original metabolically stable apelin-17 analogs with diuretic and cardiovascular effects.
The pathway of apelin and its apelin receptor (APJ) was implicated in the pathogenesis of heart failure in animal models, but a similar role in humans is unknown.
In human adults, and animals, the Apelin-APJ ligand-receptor system is emerging as having a role in the pathogenesis of cardiovascular function and heart failure.
Loss of APLN increased MI-related mortality, infarct size, and inflammation with drastic reductions in prosurvival pathways resulting in greater systolic dysfunction and heart failure.
These studies suggest that apelin-expressing endothelial cells respond to conditions associated with heart failure, possibly including local tissue hypoxia, and modulate apelin-APJ expression to regulate cardiovascular homeostasis.
The 212A variant of the APJ receptor gene for the endogenous inotrope apelin is associated with slower heart failure progression in idiopathic dilated cardiomyopathy.
Total apelin protein levels increased with ischemic heart failure as demonstrated by enzyme immunoassay (12.0+/-4.6 vs. 1.0+/-1.2 ng/ml, n=5, p=0.006) and western blot (1579400+/-477733 vs. 943000+/-157600 intensity units, n=10, p=0.008).