Poster Topical Area: Dietary Bioactive Components

Location: Hall D

Poster Board Number: 278

P08-020 - Emodin inhibits pathological cardiac hypertrophy via inhibition of histone deacetylase activity.

Monday, Jun 11
8:00 AM – 3:00 PM

Objectives: Diet is a central pathogenetic element for the development of heart disease and heart failure. Indeed, studies have linked diet to regulation of genes that promote pathological cardiac enlargement. Emerging data suggest this diet-gene interaction is mediated by epigenetic regulation. The study objective was to test the hypothesis that dietary histone deacetylase (HDAC) inhibitors stop pathological cardiac hypertrophy via epigenetic regulation of gene expression.

To test our postulate, we used neonatal rat ventricular myocytes (NRVMs) stimulated with phenylephrine (PE, 10 μM) or phorbol myristate acetate (PMA, 50 nM) to induce receptor- or intracellular-mediated pathological cardiac hypertrophy. NRVMs were further co-treated with vehicle or one of 18 dietary HDAC inhibitors (10 μM) previously identified by our lab. The classic pan-HDAC inhibitor Trichostatin A (TSA, 200 nM) was used as a positive control. NRVMs were treated for 48 hours. Cells were then fixed for immunostaining of cell size, lysed for protein expression examining HDAC activity and histone acetylation or isolated for RNA for RNA sequencing and quantitative PCR. A minimum of three experiments, with an n>3 per group was performed and data was quantified and normalized per standard procedure. One-way ANOVA with Tukey's post-hoc was performed. P≤0.05 was considered significant.

Of the 18 dietary compounds, six attenuated pathological cardiac hypertrophy in response to PE and PMA. However, only Emodin significantly inhibited HDAC activity that corresponded to increased histone acetylation in NRVMs. Similar to the classic pan-HDAC inhibitor TSA, Emodin attenuated hypertrophic gene expression, suggesting an epigenetic role for this bioactive compound. Of note, rhubarb, which is enriched in emodin was also found to inhibit cardiac hypertrophy and HDAC activity in NRVMs.

Five-year mortality rates following heart failure diagnosis approximate 50%, highlighting a critical need for improved therapeutic strategies. Findings from our study highlight Emodin and Emodin-enriched foods as cardioprotective via epigenetic regulation of global gene expression. Thus, these data point to epigenetic modifiers in our diet that have the potential to prevent or treat heart disease.

Funding Source: This work is supported by the USDA National Institute of Food and Agriculture (Hatch-NEV00727) and the Dennis Meiss & Janet Ralston Fund for Nutri-epigenetic Research to B.S.F. Core facilities used for Research were supported by National Institute of General Medical Sciences of the National Institutes of Health under grant number P20 GM103554.

CoAuthors: Leah Burnett – University of Nevada, Reno; Bradley Ferguson – University of Nevada, Reno

Levi W. Evans

University of Nevada, Reno
Reno, Nevada