This model depicts possible actions (indicated by question marks) of curcumin, including direct inhibition of p300-HAT activity and inhibition of p300 acetylation of GATA4, MEF2C, or NF-κB. p300 functions with GATA4 and MEF2C to activate hypertrophic pathways and may function with NF-κB to drive pathways important in cardiac fibrosis. Class 2 HDACs interfere with the action of MEF2C and oppose cardiac hypertrophy, while class 1 HDACs have been postulated to inhibit antihypertrophic or protective pathways. Curcumin could potentially inhibit the ability of p300 or other factors to activate class 1 HDACs. In this issue of the JCI, Li et al. (9) and Morimoto et al. (10) demonstrate that curcumin can block cardiac hypertrophy in rodent models. Correlative data suggests that possible mechanisms of action may include inhibition of p300-HAT activity and/or inhibition of GATA4 acetylation with subsequent alterations in GATA4 activity and recruitment of p300.