The ω‐3 fatty acids exert as an antioxidant via the G protein‐coupled receptor 120 (GPR120). Icosapent ethyl, a purified eicosapentaenoic acid, showed a marked reduction in sudden cardiac death. Connexin43 is sensitive to redox status. We assessed whether icosapent ethyl attenuates fatal arrhythmias after myocardial infarction, a status of high oxidative stress, through increased connexin43 expression and whether the GPR120 signalling is involved in the protection. Male Wistar rats after ligating coronary artery were assigned to either vehicle or icosapent ethyl for 4 weeks. The postinfarction period was associated with increased oxidative‐nitrosative stress. In concert, myocardial connexin43 levels revealed a significant decrease in vehicle‐treated infarcted rats compared with sham. These changes of oxidative‐nitrosative stress and connexin43 levels were blunted after icosapent ethyl administration. Provocative arrhythmias in the infarcted rats treated with icosapent ethyl were significantly improved than vehicle. Icosapent ethyl significantly increased GPR120 compared to vehicle after infarction. The effects of icosapent ethyl on superoxide and connexin43 were similar to GPR120 agonist GW9508. Besides, the effects of icosapent ethyl on oxidative‐nitrosative stress and connexin43 phosphorylation were abolished by administering AH‐7614, an inhibitor of GPR120. SIN‐1 abolished the Cx43 phosphorylation of icosapent ethyl without affecting GPR120 levels. Taken together, chronic use of icosapent ethyl after infarction is associated with up‐regulation of connexin43 phosphorylation through a GPR120‐dependent antioxidant pathway and thus plays a beneficial effect on arrhythmogenic response to programmed electrical stimulation.

中文翻译：

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二十碳五烯酸乙酯对梗塞后大鼠心脏室性心律失常易感性的影响：GPR120 介导的连接蛋白 43 磷酸化的作用。

ω-3 脂肪酸通过 G 蛋白偶联受体 120 (GPR120) 作为抗氧化剂发挥作用。二十碳五烯酸（一种纯化的二十碳五烯酸）可显着降低心脏性猝死的发生率。Connexin43 对氧化还原状态敏感。我们评估了二十碳五烯基是否通过增加连接蛋白 43 表达以及 GPR120 信号是否参与保护来减轻心肌梗塞后的致命心律失常（一种高氧化应激状态）。结扎冠状动脉后的雄性 Wistar 大鼠被分配到载体或 icosapentethyl 4 周。梗死后时期与氧化-亚硝化应激增加有关。一致地，与假手术相比，载体治疗的梗塞大鼠的心肌连接蛋白 43 水平显着降低。二十碳五烯乙酯给药后，氧化-亚硝化应激和连接蛋白43水平的这些变化减弱。用二十碳五烯乙酯治疗的梗塞大鼠的诱发性心律失常比媒介物显着改善。与梗塞后的载体相比，二十碳五烯基显着增加了 GPR120。二十碳五烯基对超氧化物和连接蛋白 43 的影响与 GPR120 激动剂 GW9508 相似。此外，通过给予 GPR120 抑制剂 AH-7614，二十碳五烯酸乙酯对氧化亚硝化应激和连接蛋白 43 磷酸化的影响被消除。SIN-1 消除了二十碳五烯基的 Cx43 磷酸化而不影响 GPR120 水平。综合起来，