Dose-dependent blockade to cardiomyocyte hypertrophy by histone deacetylase inhibitors

Christopher L. Antos, Timothy A. McKinsey, Matthew Dreitz, Lisa M. Hollingsworth, Chun Li Zhang, Kathy Schreiber, Hansjorg Rindt, Richard J. Gorczynski, Eric N. Olson

Research output: Contribution to journalArticlepeer-review

230 Scopus citations


Postnatal cardiac myocytes respond to stress signals by hypertrophic growth and activation of a fetal gene program. Recently, we showed that class II histone deacetylases (HDACs) suppress cardiac hypertrophy, and mice lacking the class II HDAC, HDAC9, are sensitized to hypertrophic signals. To further define the roles of HDACs in cardiac hypertrophy, we analyzed the effects of HDAC inhibitors on the responsiveness of primary cardiomyocytes to hypertrophic agonists. Paradoxically, HDAC inhibitors imposed a dose-dependent blockade to hypertrophy and fetal gene activation. We conclude that distinct HDACs play positive or negative roles in the control of cardiomyocyte hypertrophy. HDAC inhibitors are currently being tested in clinical trials as anti-cancer agents. Our results suggest that these inhibitors may also hold promising clinical value as therapeutics for cardiac hypertrophy and heart failure.

Original languageEnglish (US)
Pages (from-to)28930-28937
Number of pages8
JournalJournal of Biological Chemistry
Issue number31
StatePublished - Aug 1 2003

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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