• Peiran Yang, Janet J Maguire, and Anthony P Davenport.
• Experimental Medicine and Immunotherapeutics, Level 6 Addenbrooke's Centre for Clinical Investigation, Box 110 Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
• Trends Pharmacol. Sci. 2015 Sep 1; 36 (9): 560-7.

AbstractApelin and its G protein-coupled receptor (GPCR) have emerged as a key signalling pathway in the cardiovascular system. The peptide is a potent inotropic agent and vasodilator. Remarkably, a peptide, Elabela/Toddler, that has little sequence similarity to apelin, has been proposed as a second endogenous apelin receptor ligand and is encoded by a gene from a region of the genome previously classified as 'non-coding'. Apelin is downregulated in pulmonary arterial hypertension and heart failure. To replace the missing endogenous peptide, 'biased' apelin agonists have been designed that preferentially activate G protein pathways, resulting in reduced β-arrestin recruitment and receptor internalisation, with the additional benefit of attenuating detrimental β-arrestin signalling. Proof-of-concept studies support the clinical potential for apelin receptor biased agonists. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

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