ASC Methylation and Interleukin-1[beta] Are Associated with Aerobic Capacity in Heart Failure.

Background: Aerobic capacity, as measured by peak oxygen uptake (V[Combining Dot Above]O2), is one of the most powerful predictors of prognosis in heart failure (HF). Inflammation is a key factor contributing to alterations in aerobic capacity, and interleukin (IL)-1 cytokines are implicated in this process. The adaptor protein ASC is necessary for inflammasome activation of IL-1[beta] and IL-18. ASC expression is controlled through epigenetic modification; lower ASC methylation is associated with worse outcomes in HF. The purpose of this study is to examine the relationships between ASC methylation, IL-1[beta], and IL-18 with peak V[Combining Dot Above]O2 in persons with HF. Methods: This study examined the relationship between ASC methylation, IL-1[beta], and IL-18 with peak V[Combining Dot Above]O2 in 54 stable outpatients with HF. All participants were NYHA class II or III, not engaged in an exercise program, and physically able to complete an exercise treadmill test. Results: Mean peak V[Combining Dot Above]O2 was 16.68 +/- 4.7 ml/kg/min. Peak V[Combining Dot Above]O2 was positively associated with mean percent ASC methylation (r=.47, p=.001) and negatively associated with IL-1[beta] (r=-.38, p=.007). Multiple linear regression models demonstrated that peak V[Combining Dot Above]O2 increased by 2.30 ml/kg/min for every 1% increase in ASC methylation and decreased by 1.91 ml/kg/min for every 1 pg/mL increase in plasma IL-1[beta]. Conclusions: Mean percent ASC methylation and plasma IL-1[beta] levels are associated with clinically meaningful differences in peak V[Combining Dot Above]O2 in persons with HF. Inflammasome activation may play a mechanistic role in determining aerobic capacity. ASC methylation is a potentially modifiable mechanism for reducing the inflammatory response, thereby improving aerobic capacity in HF. (C) 2017 American College of Sports Medicine

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