Histone deacetylase inhibition in the treatment of heart disease.
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.
Berry
Jeff M
JM
University of Texas Southwestern Medical Center, Donald W Reynolds Cardiovascular Clinical Research Center, Dallas, Texas, USA.
Cao
Dian J
DJ
Rothermel
Beverly A
BA
Hill
Joseph A
JA
D000818:Animals; D002986:Clinical Trials as Topic / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D006331:Heart Diseases / Q000188:drug therapy* / Q000201:enzymology*; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans
D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases