Roles and Targets of Class I and IIa Histone Deacetylases in Cardiac Hypertrophy

Figure 1

The signaling cascade of class I and IIa HDACs in the development of cardiac hypertrophy. Class I HDACs can be regulated by the Hopx/HDAC2/HSP70/KLF4 pathway. Cardiac hypertrophy is induced in Hopx transgenic mice through the recruitment of HDAC2. Hypertrophic stresses including pressure overload or agonist-induced HSP70 expression are followed by its association with HDAC2. The resultant increase in HDAC2 activity decreases the expression of anti-hypertrophic mediators including KLF4 and Inpp5f. This diagram is adapted from the works of Kook et al. [20] and Kee et al. [32, 38] (JCI, 2003; Circulation Research, 2008; JMCC, 2009). Class II HDACs can be activated by PKD or CaMK. They interact with MEF2. MEF2 also associates with GATA4 and NFAT transcription factor. NFAT can be triggered by calcineurin. Class IIa HDACs can repress cardiac hypertrophy through MEF2 either directly or indirectly.