Histone deacetylase inhibition in the treatment of heart disease

Abstract

Recent work has demonstrated the importance of chromatin remodeling, especially histone acetylation, in the control of gene expression in the heart. Studies in preclinical models suggest that inhibition of histone deacetylase (HDAC) activity – using compounds that show promise in ongoing oncology trials – blunts pathologic growth of cardiac myocytes. Indeed, small-molecule inhibitors of HDACs are members of an evolving class of pharmacologic agents in development for the treatment of several diseases. If proved effective in the treatment of heart disease, HDAC inhibitors could have a significant impact on public health, as cardiovascular disease remains the leading cause of death in the US. This paper reviews understanding of the mechanisms of action of HDAC inhibitors in the heart and summarizes emerging data regarding their effects on disease-related cardiac remodeling and function.

Keywords::

• cardiac hypertrophy
• fibrosis
• heart failure
• histone deacetylases
• remodeling

Acknowledgements

The authors thank E Olson for critical reading of the manuscript. This work was supported by grants from the Donald W Reynolds Cardiovascular Clinical Research Center, NIH and AHA.

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