ROCK1 Plays a Crucial Role to Maintain Cardiac Function in Response to Pressure-Overload in Mice

acetylation by p300 histone acetyltransferase (HAT) activity was associated with GATA4 transcriptional activity, as well as pathological cardiomyocyte hypertrophy and the development of heart failure in vivo. However, little is known to what extent histone modifications can directly impact on cardiac hypertrophy. Aims: We hypothesized that the epigenetic histone modifications relate to cardiac hypertrophic responses. Methods and Results: In cardiomyocytes, phenylephrine (PE) stimulus increased the acetylation among H3K122, H3K9, and H3K14. These acetylations were significantly inhibited by knockdown of p300 and curcumin, a p300 specific HAT inhibitor. Chromatin-immunoprecipitation assay demonstrated that PE stimulus increased the recruitment of the acetylated H3K122 and H3K9 onto ANF and BNP promoters containing the GATA element. Moreover, we utilized in vivo ChIP assays with Dahl salt-sensitive rats and found that acetylation and H3K9 were increased around ANF and BNP promoters at the LVH stage and those of H3K122 were increased at the CHF stage. Conclusion: This study indicate that epigenetic hypertrophic responses via acetylations of tail and globular domains of histone were involved in the transition from LVH to CHF.