Zhang Yan, Yang Shuwen, Fu Jing, Liu Annan, Liu Deping, Cao Suyan
Department of General Practice/VIP Medical Service, Beijing Hospital, National Center of Gerontology, Beijing, China.
Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China.
J Cell Mol Med. 2020 Dec;24(23):13660-13668. doi: 10.1111/jcmm.15816. Epub 2020 Nov 1.
Obesity is a significant risk factor for atrial fibrillation (AF), which is the most common sustained arrhythmia with increased mortality and morbidity. High-fat diet (HFD)-induced obesity is associated with the activation of endoplasmic reticulum stress (ERS). However, the role of ERS in HFD-induced AF remains elusive. Human atrium samples were examined for the ERS activation test. C57BL/6J mice were divided into four groups, including the control group, the HFD group, the 4-phenylbutyric acid (4-PBA) group, and the HFD + 4-PBA group. At the age of 4 weeks, the HFD group and the HFD + 4-PBA group were given HFD to construct the obesity model, while the other two groups were given a normal diet (ND). Transesophageal programmed electrical stimulation was conducted to evaluate the AF inducibility and duration. Atrial fibrosis and ERS activation were also investigated.We found that CHOP and GRP-78 protein were significantly higher in overweight patients than the controls (both P < 0.05). AF inducibility and duration of the HFD group were significantly higher than the other groups (both P < 0.05), while there was no difference between those groups (P > 0.05). The mice of the HFD group had significantly higher collagen volume fraction (CVF%) than the other groups (P < 0.05). ERS marker protein of GRP78, p-PERK, ATF6 and CHOP protein expression level was increased in the HFD group, which were significantly mitigated in the HFD + 4-PBA group. In summary, HFD-induced ERS activation facilitates atrial fibrosis and AF. The inhibition of ERS might alleviate atrial fibrosis and reduce the incidence of AF-associated obesity.
肥胖是心房颤动（AF）的一个重要风险因素，心房颤动是最常见的持续性心律失常，死亡率和发病率均有所增加。高脂饮食（HFD）诱导的肥胖与内质网应激（ERS）的激活有关。然而，ERS在HFD诱导的AF中的作用仍不清楚。对人体心房样本进行了ERS激活测试。将C57BL/6J小鼠分为四组，包括对照组、HFD组、4-苯基丁酸（4-PBA）组和HFD + 4-PBA组。在4周龄时，HFD组和HFD + 4-PBA组给予HFD以构建肥胖模型，而其他两组给予正常饮食（ND）。进行经食管程控电刺激以评估AF的诱导性和持续时间。还研究了心房纤维化和ERS激活情况。我们发现，超重患者的CHOP和GRP-78蛋白显著高于对照组（均P < 0.05）。HFD组的AF诱导性和持续时间显著高于其他组（均P < 0.05），而这些组之间无差异（P > 0.05）。HFD组小鼠的胶原容积分数（CVF%）显著高于其他组（P < 0.05）。HFD组中GRP78、p-PERK、ATF6和CHOP蛋白表达水平等ERS标志物蛋白增加，而在HFD + 4-PBA组中显著减轻。总之，HFD诱导的ERS激活促进心房纤维化和AF。抑制ERS可能减轻心房纤维化并降低与肥胖相关的AF的发生率。
