Exosomal microRNA-194 causes cardiac injury and mitochondrial dysfunction in obese mice
Exosomal microRNA-194 causes cardiac injury and mitochondrial dysfunction in obese mice
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DOI：
10.1016/j.bbrc.2018.08.113
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发表时间：
2018-09-18
影响因子：
3.1
通讯作者：
Zhou, Yiwen
中科院分区：
文献类型：
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作者：
Nie, Hezhongrong;Pan, Yong;Zhou, Yiwen
肥胖与心血管发病率和死亡率增加相关，但循环因素对心功能的影响尚未完全阐明。本研究旨在探讨微小RNA（miR）-194（一种肝脏富集的miR）在人类受试者和小鼠肥胖相关心肌病过程中的病理生理学作用。在 39 名瘦人和 35 名肥胖人类受试者中测量了循环外泌体 miR-194 的表达水平，并与心脏参数相关。通过在小鼠心肌细胞和肥胖相关心肌病中施用 miR-194 海绵，研究了 miR-194 对线粒体活性和心脏功能的影响。循环miR-194水平的上调与人类心脏功能受损密切相关，包括射血分数（r = -0.5002，p < 0.01）和NT-proBNP水平（r = 03670，p < 0.01）。肥胖小鼠的外泌体损害了肌细胞线粒体]活性，但用 miR-194 海绵阻断可减弱外泌体 miR-194 诱导的 ATP 产生 (p < 0.05)、基础耗氧量 (p < 0.01) 和线粒体复合物 I 活性 (p < 0.01) 的减少。
Obesity is associated with increased cardiovascular morbidity and mortality, but the effects of circulating factors on cardiac function is not fully elucidated. Present study aims to explore the pathophysiological role of microRNA (miR)-194, one of hepatic enriched miRs, in the process of obesity-related cardiomyopathy in human subjects and mice. The expression level of circulating exosomal miR-194 was measured in 39 lean and 35 obese human subjects, and correlated with cardiac parameters. The effects of miR-194 on mitochondrial activity and cardiac function were investigated by administration of miR-194 sponge in mouse cardiomyocytes and obesity-related cardiomyopathy. The upregulation of circulating miR-194 level was closely correlated with impaired human cardiac function, including ejection fraction (r = -0.5002, p < 0.01) and NT-proBNP levels (r = 03670, p < 0.01). Exosomes from obese mice impaired myocyte mitochondria] activity, but blocking with miR-194 sponge attenuated the exosomal miR-194-induced reduction of ATP production (p < 0.05), basal oxygen consumption (p < 0.01) and mitochondrial complex I activity (p