TY - JOUR
T1 - Dose-dependent blockade to cardiomyocyte hypertrophy by histone deacetylase inhibitors
AU - Antos, Christopher L.
AU - McKinsey, Timothy A.
AU - Dreitz, Matthew
AU - Hollingsworth, Lisa M.
AU - Zhang, Chun Li
AU - Schreiber, Kathy
AU - Rindt, Hansjorg
AU - Gorczynski, Richard J.
AU - Olson, Eric N.
PY - 2003/8/1
Y1 - 2003/8/1
N2 - 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.
AB - 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.
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U2 - 10.1074/jbc.M303113200
DO - 10.1074/jbc.M303113200
M3 - Article
C2 - 12761226
AN - SCOPUS:0041530268
SN - 0021-9258
VL - 278
SP - 28930
EP - 28937
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 31
ER -