TY - GEN
T1 - Control of cardiac hypertrophy and heart failure by histone acetylation/deacetylation
AU - Olson, Eric N.
AU - Backs, Johannes
AU - McKinsey, Timothy A.
PY - 2006
Y1 - 2006
N2 - The adult heart responds to acute and chronic stresses by a remodelling process that is accompanied by myocyte hypertrophy, impaired contractility, and pump failure, often culminating in sudden death. Pathological growth and remodelling of the adult heart is often associated with the reactivation of a fetal cardiac gene program that further weakens cardiac performance. Recent studies have revealed key roles for histone deacetylases (HDACs) in the control of pathological cardiac growth. Class II HDACs associate with the MEF2 transcription factor, and other factors, to maintain normal cardiac size and function. Stress signals lead to the phosphorylation of class II HDACs and their export from the nucleus to the cytoplasm, with consequent activation of genes involved in cardiac growth. HDAC knockout mice are hypersensitive to stress signalling and develop massively enlarged hearts in response to various pathological stress stimuli due to an inability to counteract pathological signalling to MEF2. Strategies for normalizing gene expression in the failing heart by regulating HDAC phosphorylation and function represent potentially powerful therapeutic approaches.
AB - The adult heart responds to acute and chronic stresses by a remodelling process that is accompanied by myocyte hypertrophy, impaired contractility, and pump failure, often culminating in sudden death. Pathological growth and remodelling of the adult heart is often associated with the reactivation of a fetal cardiac gene program that further weakens cardiac performance. Recent studies have revealed key roles for histone deacetylases (HDACs) in the control of pathological cardiac growth. Class II HDACs associate with the MEF2 transcription factor, and other factors, to maintain normal cardiac size and function. Stress signals lead to the phosphorylation of class II HDACs and their export from the nucleus to the cytoplasm, with consequent activation of genes involved in cardiac growth. HDAC knockout mice are hypersensitive to stress signalling and develop massively enlarged hearts in response to various pathological stress stimuli due to an inability to counteract pathological signalling to MEF2. Strategies for normalizing gene expression in the failing heart by regulating HDAC phosphorylation and function represent potentially powerful therapeutic approaches.
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M3 - Conference contribution
C2 - 17019803
AN - SCOPUS:36148962539
SN - 9780470015971
T3 - Novartis Foundation Symposium
SP - 3
EP - 12
BT - Heart Failure
ER -