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Background--How canonical Wnt/β-catenin signals in adult hearts, especially in different diseased states, remains unclear. The proto-oncogene, c-Myc, is a Wnt target and an early response gene during cardiac stress. It is not clear whether c-Myc is activated or how it is regulated during heart failure. Methods and Results--We investigated canonical Wnt/ß-catenin signaling and how it regulated c-Myc expression in failing hearts of human ischemic heart disease, idiopathic dilated cardiomyopathy, and murine desmin-related cardiomyopathy. Our data demonstrated that canonical Wnt/β-catenin signaling was activated through nuclear accumulation of β-catenin in idiopathic dilated cardiomyopathy, ischemic heart disease, and murine desmin-related cardiomyopathy when compared with nonfailing controls and transcription factor 7-like 2 (TCF7L2) was the main β-catenin partner of the T-cell factor (TCF) family in adult hearts. We further revealed that c-Myc mRNA and protein levels were significantly elevated in failing hearts by real-time reverse transcription polymerase chain reaction, Western blotting, and immunohistochemical staining. Immunoprecipitation and confocal microscopy further showed that β-catenin interacted and colocalized with TCF7L2. More importantly, chromatin immunoprecipitation confirmed that β-catenin and TCF7L2 were recruited to the regulatory elements of c-Myc. This recruitment was associated with increased histone H3 acetylation and transcriptional upregulation of c-Myc. With lentiviral infection, TCF7L2 overexpression increased c-Myc expression and cardiomyocyte size, whereas shRNA-mediated knockdown of TCF7L2 suppressed c-Myc expression and cardiomyocyte growth in cultured neonatal rat cardiomyocytes. Conclusions--This study indicates that TCF7L2 mediates canonic Wnt/β-catenin signaling and c-Myc upregulation during abnormal cardiac remodeling in heart failure and suppression of Wnt/β-catenin to c-Myc axis can be explored for preventing and treating heart failure. [ABSTRACT FROM AUTHOR]

The article discusses the study which aims to examine the role of cyclic nucleotide phosphodiesterases (PDE1) in balancing intracellular cardiomyocyte hypertrophy and cyclic guanosine monophosphate (cGMP). In the process, PDE1A used small interfering RNA to neonatal and adult rat ventricular myocytes in determining the chronic isoproterenol infusion in vivo in human hearts. Thus, PDE1A reduced the intracellular cGMP and cGMP-dependent protein kinase towards cardiomyocyte hypertrophy.

The article presents a study on the role of reactive oxygen species-induced activation of p90 ribosomal S6 kinase (p90RSK) in cardiac repolarization. It mentions arrhythmias, hydrogen peroxide, phosphorylation, and currents to expound on the study. This study suggests that p90RSK prolongs cardiac repolarization through the inhibition of outward K+ channel activity.