The novel GPCR peptide ligand Elabela/Toddler (APELA, Ela), first identified in the fish Danio and critical for the development of the heart, has now been identified in the human cardiovascular system. Yang et al.  have recently showed that the peptide binds to the apelin receptor in human heart. Using in silico molecular modeling and docking, they proposed a binding mode of ELA to the apelin receptor (APLNR) that is consistent with competition binding experiments. The paper also shows peptide binding is blocked by apelin receptor antagonists and comparable to apelin, increased cardiac output and elicited vasodilatation in rats in vivo. Ela expression was reduced in cardiopulmonary tissues from patients with pulmonary arterial hypertension (PAH) and animal models. However, daily injections of Ela to replace the missing peptide, attenuated the development of PAH in an animal model of this disease, suggesting this could be a potential target for translational research.
 Yang et al. (2017). Elabela/Toddler Is an Endogenous Agonist of the Apelin APJ Receptor in the Adult Cardiovascular System, and Exogenous Administration of the Peptide Compensates for the Downregulation of Its Expression in Pulmonary Arterial Hypertension. Circulation, 135(12):1160-1173. [PMID: 28137936]
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