Cardiac hypertrophy and histone deacetylase–dependent transcriptional repression mediated by the atypical homeodomain protein Hop
J. Clin. Invest. Hyun Kook, et al. 112:863 doi:10.1172/JCI19137 [Go to this article.]

Figure 4
Treatment with HDAC inhibitor prevents cardiac hypertrophy in Hop transgenic mice. (a) HDAC activity was associated with immunoprecipitated transgenic Hop protein derived from hearts of transgenic Hop mice (5–6 weeks of age) when compared with wild-type littermates. (b) Transgenic and wild-type littermates were treated with daily injections of TSA between the ages of 3 and 5 weeks. Heart weight–to–body weight ratios were calculated at 5 weeks. Bars indicate mean of values shown, and each filled circle represents one animal. TSA significantly attenuated cardiac hypertrophy, but did not affect heart weight–to–body weight ratio in nontransgenic mice. (c) Hop transgenic mice were also treated with sodium valproate between 3 and 5 weeks of age, which resulted in attenuation of cardiac enlargement at 5 weeks. (d) Wild-type mice were treated with isoproterenol (ISO) infusion between 3 and 5 weeks of life, with or without daily injection of TSA. Heart weight–to–body weight ratio increased significantly with isoproterenol, and this increase was significantly inhibited by TSA. (e) Model depicting the ability of Hop or other hypertrophic stimuli to recruit class I HDACs resulting in inhibition of antihypertrophic gene programs. Inducers of cardiac hypertrophy are also thought to function by altering calcium homeostasis or mechanical stretch and induce prohypertrophic genes. Class II HDACs can inhibit some prohypertrophic programs. The relative balance of pro- and antihypertrophic gene programs will determine the extent of myocyte hypertrophy.