Selective phosphorylation of PKA targets after beta-adrenergic receptor stimulation impairs myofilament function in Mybpc3-targeted HCM mouse model

摘要

Aims Hypertrophic cardiomyopathy (HCM) has been associated with reduced p-adrenergic receptor (beta-AR) signalling, leading downstream to a low protein kinase A (PKA)-mediated phosphorylation. It remained undefined whether all PKA targets will be affected similarly by diminished beta-AR signalling in HCM. We aimed to investigate the role of beta-AR signalling on regulating myofilament and calcium handling in an HCM mouse model harbouring a gene mutation (G > A transition on the last nucleotide of exon 6) in Mybpc3 encoding cardiac myosin-binding protein C.