Effects of Exercise on ASC Methylation and IL-1 Cytokines in Heart Failure

Introduction/Purpose Inflammation contributes to heart failure (HF) progression and the interleukin (IL)-1 cytokine IL-1β is implicated in this process. The adaptor protein ASC is necessary for inflammasome activation of IL-1β. Lower ASC methylation is associated with worse outcomes in HF. The purpose of this study was to examine the effects of exercise on changes in ASC methylation and activation of the interleukin-1 family cytokine IL-1β in persons with HF. Methods Participants (N=54) were randomized to receive exercise intervention (n=38) or attention control (n=16) for 3 months. Percent methylation of the ASC gene, plasma IL-1β, and ASC mRNA and were obtained at baseline, 3 months, and 6 months. Results ASC methylation was higher in the exercise group as compared to control at 3 months (6.10±0.5% vs. 5.80±0.4%; p=.04) and 6 months (6.07±0.4 vs. 5.82±0.4; p=.04). Plasma IL-1β was lower in the exercise group at 3 months (1.43±0.5 pg/mL vs. 2.09±1.3 pg/mL; p=.02) and 6 months (1.49±0.5 pg/mL vs. 2.13±1.4 pg/mL; p=.004). ASC mRNA expression was negatively associated with ASC methylation at baseline (r=-.97, p=.001), 3 months (r=-.90, p=.001), and 6 months (r=-.81, p=.001). ASC mRNA was lower than baseline at 3 months (p=.004) and 6 months (p=.002) among those in the exercise group. ASC methylation was positively associated with six-minute walk test (6MWT) at baseline (r=.517, p<.001 months p=".004)," and conclusions exercise was related to increased mean percent asc methylation decreased il-1 mrna gene expression in hf. epigenetic regulation of can be a biological mechanism by which promote better outcomes supported part national institutes health institute nursing research grant number r. gary the heart failure society america b. butts center for advancing translational sciences under award ul1tr000454. effort funded numbers t32nr012715 s. dunbar content is solely responsibility authors does not necessarily represent official views health. results this study are presented clearly honestly without fabrication falsification or inappropriate data manipulation. present do constitute endorsement acsm. conflicts interest: none bb rg ec sd. jb consultant amgen bayer cardiocell celladon novartis stealth peptide relypsa z pharma trevena zensun. accepted publication: april american college sports medicine>

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