Effects of Exercise on ASC Methylation and IL-1 Cytokines in Heart Failure.
Effects of Exercise on ASC Methylation and IL-1 Cytokines in Heart Failure.
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DOI：
10.1249/mss.0000000000001641
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发表时间：
2018-09
影响因子：
4.1
通讯作者：
Gary RA
中科院分区：
文献类型：
--
作者：
Butts B;Butler J;Dunbar SB;Corwin E;Gary RA
炎症有助于心力衰竭（HF）的进展，白细胞介素(IL)-1细胞因子IL-1β参与了这一过程。适配蛋白ASC是炎性小体激活IL-1β所必需的。较低的ASC甲基化与心衰患者较差的预后相关。本研究的目的是研究运动对心衰患者ASC甲基化变化和白细胞介素-1家族细胞因子IL-1β活化的影响。参与者（N=54）被随机分为运动干预组（N= 38）和注意力控制组（N= 16），为期3个月。在基线、3个月和6个月时获得ASC基因、血浆IL-1β和ASC mRNA的甲基化百分比。运动组ASC甲基化在3个月（6.10±0.5%比5.80±0.4%,p= 0.04）和6个月（6.07±0.4比5.82±0.4,p= 0.04）时高于对照组。运动组血浆IL-1β在3个月（1.43±0.5 pg/mL比2.09±1.3 pg/mL, p= 0.02）和6个月（1.49±0.5 pg/mL比2.13±1.4 pg/mL, p= 0.004）时较低。基线时ASC mRNA表达与ASC甲基化呈负相关（r=−）。97, p=.001)， 3个月(r= -。90, p=.001)， 6个月(r= -。81年,p =措施)。运动组ASC mRNA在3个月（p= 0.004）和6个月（p= 0.002）时均低于基线。ASC甲基化在基线（r= 0.517, p< 0.001）、3个月（r= 0.464, p= 0.004）和6个月（r=497, p= 0.05）时与6分钟步行试验（6MWT）呈正相关。运动与HF中ASC甲基化平均百分比增加、IL-1β和ASC mRNA基因表达降低有关。ASC的表观遗传调控可能是一种生物学机制，通过这种机制，运动可以促进心衰患者更好的预后。
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. 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. 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), 3 months (r=.464, p=.004), and 6 months (r=497, p=.05). Exercise was related to increased mean percent ASC methylation and decreased IL-1β and ASC mRNA gene expression in HF. Epigenetic regulation of ASC can be a biological mechanism by which exercise can promote better outcomes in HF.