Control of cardiac hypertrophy and heart failure by histone acetylation/deacetylation

Eric N. Olson, Johannes Backs, Timothy A. McKinsey

Research output: Chapter in Book/Report/Conference proceedingConference contribution

52 Scopus citations

Abstract

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.

Original languageEnglish (US)
Title of host publicationNovartis Foundation Symposium
Pages3-12
Number of pages10
Volume274
Publication statusPublished - 2006

Publication series

NameNovartis Foundation Symposium
Volume274
ISSN (Print)15282511

    Fingerprint

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Olson, E. N., Backs, J., & McKinsey, T. A. (2006). Control of cardiac hypertrophy and heart failure by histone acetylation/deacetylation. In Novartis Foundation Symposium (Vol. 274, pp. 3-12). (Novartis Foundation Symposium; Vol. 274).