Cardiac myosin light chain phosphorylation and inotropic effects of a biased ligand, XXXX , in a @entity384 model.

@entity308 @entity19 @entity384 @entity1184 @entity70692 @entity9886 @entity49819 @entity141 @entity943 @entity14207
AIMS: Therapeutic approaches to treat @entity384 ( @entity384 ), which is characterized by @entity308 and susceptibility to @entity141 -related @entity943 , have been generally unsuccessful. Our objective in the present work was to determine the effect of the @entity14207 ( @entity14207 ) biased ligand, @entity70692 , on contractility of hearts of a transgenic @entity19 model of @entity384 with mutation in tropomyosin at position 54 (TG- @entity49819 ). Our rationale is based on previous studies, which have supported the hypothesis that biased G-protein-coupled receptor ligands, signalling via b-arrestin, increase cardiac contractility with no effect on @entity141 transients. Our previous work demonstrated that the biased ligand @entity70692 is able to block angiotensin-induced @entity1184 , while promoting an increase in sarcomere @entity141 response. METHODS AND RESULTS: We tested the hypothesis that the @entity308 in cardiac function associated with @entity384 can be offset by infusion of the @entity14207 biased ligand, @entity70692 . We intravenously infused saline, @entity70692 , or the unbiased ligand, @entity9886 , for 15 min in TG- @entity49819 and non- @entity19 to obtain left ventricular pressure-volume relations. Hearts were analysed for sarcomeric protein phosphorylation. Results showed that the @entity14207 biased ligand increases cardiac performance in TG- @entity49819 @entity19 in association with increased myosin light chain-2 phosphorylation. CONCLUSION: Treatment of @entity19 with an @entity14207 biased ligand, acting via b-arrestin signalling, is able to induce an increase in cardiac contractility associated with an increase in ventricular myosin light chain-2 phosphorylation. @entity14207 biased ligands may prove to be a novel inotropic approach in @entity384 .
