title: Apelin, Elabela/Toddler, and biased agonists as novel therapeutic agents in the cardiovascular system.
abstract: Apelin 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.
authors.affiliation: Experimental Medicine and Immunotherapeutics, Level 6 Addenbrooke's Centre for Clinical Investigation, Box 110 Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
authors.forename: Peiran
authors.initials: P
authors.lastname: Yang
authors.affiliation: Experimental Medicine and Immunotherapeutics, Level 6 Addenbrooke's Centre for Clinical Investigation, Box 110 Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
authors.forename: Janet J
authors.initials: JJ
authors.lastname: Maguire
authors.affiliation: Experimental Medicine and Immunotherapeutics, Level 6 Addenbrooke's Centre for Clinical Investigation, Box 110 Addenbrooke's Hospital, Cambridge CB2 0QQ, UK. Electronic address: apd10@medschl.cam.ac.uk.
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Davenport
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D008969:Molecular Sequence Data; D036361:Peptide Hormones / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D043562:Receptors, G-Protein-Coupled / Q000819:agonists
chemical_list: C000601133:APELA protein, human; D036341:Intercellular Signaling Peptides and Proteins; D036361:Peptide Hormones; D043562:Receptors, G-Protein-Coupled; C495199:apelin-13 peptide
keywords: APJ; Elabela/Toddler; apelin; apelin receptor; biased agonist; pulmonary arterial hypertension