Serum-Derived Extracellular Vesicles Protect Against Acute Myocardial Infarction by Regulating miR-21/PDCD4 Signaling Pathway.

Serum-Derived Extracellular Vesicles Protect Against Acute Myocardial Infarction by Regulating miR-21/PDCD4 Signaling Pathway.
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血清来源的细胞外囊泡通过调节 miR-21/PDCD4 信号通路预防急性心肌梗塞。

DOI:
10.3389/fphys.2018.00348
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发表时间:
2018
影响因子:
4
通讯作者:
Zhou L
Zhou L
中科院分区:
医学2区
文献类型:
--
作者:
Gu H;Liu Z;Li Y;Xie Y;Yao J;Zhu Y;Xu J;Dai Q;Zhong C;Zhu H;Ding S;Zhou L

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急性心肌梗死(AMI)是全球发病率和死亡率的主要原因。细胞外囊泡(EV)被认为是预防MI的一种有前途的治疗方法。血清是EV的丰富来源,其转运各种microRNA(miRNAs,miRs)。来自血清的EV已被证明有益于保护免受缺血再灌注损伤;然而,它们在AMI中的作用尚不清楚。此外,miRNA是否可能对血清EV预防AMI的作用负责尚不确定。在这里,我们证明了血清EV在AMI的细胞和小鼠模型中显著减少心肌细胞凋亡,并显着减弱AMI后小鼠心脏的梗死面积。miR-21的抑制显示出降低血清EV在抑制心肌细胞凋亡中的保护作用。AMI后小鼠心脏中miR-21减少,而血清EVs增加。此外,程序性细胞死亡4(PDCD 4)表达被鉴定为miR-21的靶基因。因此,我们的研究显示了血清EVs对AMI的保护作用,并为AMI的治疗提供了新的策略。
Acute myocardial infarction (AMI) represents a leading cause of morbidity and mortality worldwide. Extracellular vesicles (EVs) are being recognized as a promising therapeutic approach in protecting against MI. Serum is a rich source of EVs, which transports various microRNAs (miRNAs, miRs). EVs from serum have been shown beneficial for protecting against ischemia-reperfusion injury; however, their roles in AMI are unclear. In addition, whether a miRNA might be responsible for the effects of serum EVs on protecting against AMI is undetermined. Here, we demonstrated that serum EVs significantly reduced cardiomyocytes apoptosis in both cellular and mouse models of AMI, and dramatically attenuated the infarct size in mouse hearts after AMI. Inhibition of miR-21 was shown to reduce the protective effects of serum EVs in inhibiting cardiomyocytes apoptosis. miR-21 was decreased in mouse hearts after AMI, while serum EVs increased that. In addition, the programmed cell death 4 (PDCD4) expression was identified as a target gene of miR-21. Therefore, our study showed the protective effects of serum EVs on AMI, and provided a novel strategy for AMI therapy.
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