title: Apelin receptor: its responsiveness to stretch mechanisms and its potential for cardiovascular therapy.
abstract: It has recently been demonstrated that the apelin receptor (APJ) plays a significant role in mediating the stretch response within the heart in a G-protein-independent and β-arrestin-dependent fashion. This discovery adds to the consolidated literature describing the potential benefits of APJ agonists. In this review, the authors will examine the functional selectivity of APJ and stretch with respect to their ability to signal via both G-protein-dependent and G-protein-independent mechanisms, with a focus on the multifunctional protein, β-arrestin. The possibility of selecting or designing novel ligands that differentially activate only a subset of functions via a single receptor holds great promise for the treatment of diseases such as heart failure and hypertension. Finally, hypothetical approaches to target APJ, taking into account its downstream pathways, will be described.
authors.affiliation: Temple University School of Medicine, Philadelphia, PA, USA.
authors.forename: Maria Cecilia
authors.initials: MC
authors.lastname: Scimia
authors.forename: Benjamin E
authors.initials: BE
authors.lastname: Blass
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Koch
mesh_terms: D000818:Animals; D000075244:Apelin Receptors; D019390:Arrestins / Q000378:metabolism*; D015195:Drug Design; D019204:GTP-Binding Proteins / Q000378:metabolism; D006333:Heart Failure / Q000188:drug therapy / Q000503:physiopathology; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology; D008024:Ligands; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D000071557:beta-Arrestins
chemical_list: C104575:APLNR protein, human; D000075244:Apelin Receptors; D019390:Arrestins; D008024:Ligands; D043562:Receptors, G-Protein-Coupled; D000071557:beta-Arrestins; D019204:GTP-Binding Proteins
keywords: GPCRs; biased ligands; pluridimensional efficacy