Currying favor for the heart

Abstract

Curcumin, a commonly available spice and alternative medicine, has been tested in the laboratory and the clinic for activity against a wide range of diseases. It is thought to possess antiinflammatory and antioxidant activities and may also function to inhibit histone acetyl transferases, which activate gene expression via chromatin remodeling. Two reports in this issue of the JCI, by Morimoto et al. and Li et al., suggest that curcumin may inhibit cardiac hypertrophy in rodent models and provide beneficial effects after myocardial infarction or in the setting of hypertension (see the related articles beginning on pages 868 and 879, respectively). These results will spur further mechanistic inquiry into the role of chromatin remodeling in the regulation of cardiac homeostasis.

Figure 1. Curcumin can block cardiac hypertrophy in isolated cells and animal models, but the mechanism of action is unclear.

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.