HDAC Signaling Networks in Heart Failure
Histone modifications are mediated by multiple chromatin-modifying enzymes such as histone methyltransferases and demethylases or histone acetyltransferases and histone deacetylases (HDACs). Because of their involvement in heart muscle disease, HDACs have gained a lot of attention over the last 15 years. HDACs are divided into different classes. Among them, class IIa HDACs undergo many posttranslational modification and bind to signaling molecules and other transcriptional regulators. Thereby, class IIa HDACs play a central role in cardiac signaling networks. Understanding the specific signaling events may allow the development of pharmacological approaches other than inhibiting their enzymatic activity. Thus, targeting HDAC signaling may provide more specificity towards disease- and stress-related mechanisms, potentially leading to fewer side effects than global inhibition of HDACs.
KeywordsHDAC Inhibitor Nuclear Export Serum Response Factor Adverse Cardiac Remodel HDAC Function
J.B. was supported by grants from the Deutsche Forschungsgemeinschaft (BA 2258/2-1, SFB 1118), the European Commission (FP7-Health-2010, MEDIA-261409), H.A.K. and J.B. by the DZHK (Deutsches Zentrum für Herz-Kreislauf-Forschung—German Centre for Cardiovascular Research) and by the BMBF (German Ministry of Education and Research).
Conflict of Interest
J.B. holds a patent on epigenetic therapies, in particular, disrupting the CaMKII–HDAC4 interaction and gene therapy with HDAC4-NT and the upstream protease.
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