Inhibiting miR-22 Alleviates Cardiac Dysfunction by Regulating Sirt1 in Septic Cardiomyopathy.
Inhibiting miR-22 Alleviates Cardiac Dysfunction by Regulating Sirt1 in Septic Cardiomyopathy.
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抑制 miR-22 通过调节 Sirt1 缓解脓毒症心肌病患者的心脏功能障碍
DOI：
10.3389/fcell.2021.650666
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发表时间：
2021
影响因子：
5.5
通讯作者：
Zhang M
中科院分区：
文献类型：
--
作者：
Wang R;Xu Y;Zhang W;Fang Y;Yang T;Zeng D;Wei T;Liu J;Zhou H;Li Y;Huang ZP;Zhang M
高发病率和高死亡率是感染性心肌病最典型的特点。我们的目的是揭示miR-22在感染性心肌病中的作用，并探讨其潜在的机制。MIR-22心脏特异基因敲除小鼠(miR-22cKO)和miR-22心脏特异转基因小鼠(miR-22cOE)接受盲肠结扎和穿孔(CLP)手术，对照组采用假手术。超声心动图结果显示，miR-22cKO CLP小鼠心功能障碍明显减轻。MiR-22cKO CLP小鼠血清LDH和CK-MB明显降低。正如预期的那样，miR-22cKO CLP组小鼠的细胞凋亡减少，自噬增加，线粒体功能障碍减轻，而miR-22cOE组的作用相反。抑制miR-22通过增加Lc3II/GAPDH比值和降低p62水平来促进自噬。此外，用脂多糖(LPS)体外培养原代心肌细胞，模拟脓毒症诱导的心肌病。抑制miR-22促进自噬通量，在巴菲罗星A1条件下，通过增加LC3II/GAPDH比率和降低p62蛋白水平来证实。敲除miR-22可能通过增加自噬和通过SIRT1减少细胞凋亡而对脓毒症起到心脏保护作用。我们的结果表明，靶向miR-22可能成为感染性心肌病治疗的一种新策略。
High morbidity and mortality are the most typical characteristics of septic cardiomyopathy. We aimed to reveal the role of miR-22 in septic cardiomyopathy and to explore the underlying mechanisms. miR-22 cardiac-specific knockout (miR-22cKO) mice and miR-22 cardiac-specific transgenic (miR-22cOE) mice were subjected to a cecal ligation and puncture (CLP) operation, while a sham operation was used in the control group. The echocardiogram results suggested that miR-22cKO CLP mice cardiac dysfunction was alleviated. The serum LDH and CK-MB were reduced in the miR-22cKO CLP mice. As expected, there was reduced apoptosis, increased autophagy and alleviated mitochondrial dysfunction in the miR-22cKO CLP mice, while it had contrary role in the miR-22cOE group. Inhibiting miR-22 promoted autophagy by increasing the LC3II/GAPDH ratio and decreasing the p62 level. Additionally, culturing primary cardiomyocytes with lipopolysaccharide (LPS) simulated sepsis-induced cardiomyopathy in vitro. Inhibiting miR-22 promoted autophagic flux confirmed by an increased LC3II/GAPDH ratio and reduced p62 protein level under bafilomycin A1 conditions. Knocking out miR-22 may exert a cardioprotective effect on sepsis by increasing autophagy and decreasing apoptosis via sirt1. Our results revealed that targeting miR-22 may become a new strategy for septic cardiomyopathy treatment.
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脓毒症心肌病的线粒体机制。
影响因子：
5.6
作者：
Cimolai MC;Alvarez S;Bode C;Bugger H
通讯作者：
Bugger H
DOI：
10.1016/j.numecd.2018.06.005
发表时间：
2018-09-01
影响因子：
3.9
作者：
Feidantsis, K.;Mellidis, K.;Lazou, A.
通讯作者：
Lazou, A.
影响因子：
6.6
作者：
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通讯作者：
Sadoshima, Junichi
影响因子：
4.6
作者：
Han W;Wang H;Su L;Long Y;Cui N;Liu D
通讯作者：
Liu D
影响因子：
--
作者：
Hong, Yuan;Cao, Huaming;Chen, Xichuang
通讯作者：
Chen, Xichuang