The HDAC Inhibitor Emodin Blocks Hypertension-Induced Cardiac Hypertrophy: A Mediating Role for the Gut?

Abstract

Abstract Objectives Evidence suggests that food bioactives impact the epigenome to prevent pathological cardiac hypertrophy. Recently, we showed that emodin, an anthraquinone, attenuated pathological cardiac hypertrophy and histone deacetylase (HDAC) activity. However, we only examined the cardioprotective effects of emodin's parent compound, not of emodin metabolites or of emodin-gut microbiome interactions. The microbiome has emerged as a key player in chronic diseases such as metabolic and cardiac disease. Thus, we hypothesized that emodin could reverse hypertension-induced changes in microbial communities. Methods Normo- and hypertensive (angiotensin ii) C57/BL6 female mice were randomly assigned to receive vehicle (Veh, DMSO: PEG 1:1) or emodin (Emod, 30 mg/kg) for 14 days. Body weight was collected pre- and post-treatment and blood pressure assessed via tail-cuff. At study end, mice were euthanized and assessed for heart weight and fibrosis. In addition, stool samples and cecal content were collected to elucidate changes in microbial populations using 16S rRNA sequencing. Lastly, tissue was lysed and RNA isolated for RNA sequencing. One-way ANOVA with Tukey's post-hoc was performed unless otherwise specified and P < 0.05 considered significant. Results Emodin significantly attenuated cardiac hypertrophy and fibrosis in female mice. No significant changes were observed for body weight or systolic blood pressure in response to hypertension or emodin. Lastly, preliminary analysis suggests that hypertension altered the microbiome, with evidence to support that emodin effects gut microbiota. Conclusions Our data demonstrates that emodin attenuates pathological hypertrophy and fibrosis in female mice. Whether this attenuation in cardiac remodeling is driven, in part, by the actions of emodin on the gut the microbiome remains unclear and is currently an active topic of investigation in our lab. Funding Sources This work is supported by the USDA NIFA (Hatch-NEV00767), the Dennis Meiss & Janet Ralston Fund for Nutri-epigenetic Research, the National Institute for General Medical Sciences (NIGMS) of the NIH (P20 GM130459) and the National Heart, Lung, and Blood Institute of the NIH (R15 HL143496) to B.S.F. Core facilities used for Research were supported by NIGMS of the NIH (P20 GM103554).