Plasma exosomes induced by remote ischaemic preconditioning attenuate myocardial ischaemia/reperfusion injury by transferring miR-24.
Plasma exosomes induced by remote ischaemic preconditioning attenuate myocardial ischaemia/reperfusion injury by transferring miR-24.
复制标题
远程缺血预处理诱导的血浆外泌体通过转移 miR-24 减轻心肌缺血/再灌注损伤
DOI：
10.1038/s41419-018-0274-x
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发表时间：
2018-02-23
影响因子：
9
通讯作者：
Xiaoshu C
中科院分区：
文献类型：
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作者：
Minghua W;Zhijian G;Chahua H;Qiang L;Minxuan X;Luqiao W;Weifang Z;Peng L;Biming Z;Lingling Y;Zhenzhen W;Jianqing X;Huihui B;Xiaozhong W;Xiaoshu C
远程缺血预处理（RIPC）是众所周知的保护心肌缺血/再灌注损伤（IRI）。外泌体是一种小的细胞外囊泡，已成为细胞间通讯的关键介质。各种研究已经证实循环外泌体介导RIPC。然而，RIPC诱导的外泌体介导的心脏保护的潜在机制仍然难以捉摸。在我们的研究中，我们发现，在体内，来自经历RIPC的大鼠血浆的外泌体中miR-24的表达水平高于来自对照大鼠血浆的外泌体。大鼠血浆外泌体可被H9 c2细胞摄取。此外，miR-24存在于RIPC诱导的外泌体中，并在体外通过下调H2 O2处理的H9 c2细胞中Bim表达来减少氧化应激介导的损伤和减少凋亡。在体内，RIPC诱导的外泌体中的miR-24减少了心肌细胞凋亡，减小了梗死面积并改善了心脏功能。此外，在体外和体内，miR-24的凋亡减少作用被miR-24抑制剂或抑制剂抵消。因此，我们提供的证据表明，RIPC诱导的外泌体可以通过旁分泌方式转移miR-24来减少细胞凋亡，并且外泌体中的miR-24在介导RIPC的保护作用中起着核心作用。
Remote ischaemic preconditioning (RIPC) is well known to protect the myocardium against ischaemia/reperfusion injury (IRI). Exosomes are small extracellular vesicles that have become the key mediators of intercellular communication. Various studies have confirmed that circulating exosomes mediate RIPC. However, the underlying mechanisms for RIPC-induced exosome-mediated cardioprotection remain elusive. In our study, we found that the expression level of miR-24 was higher in exosomes derived from the plasma of rats subjected to RIPC than in exosomes derived from the plasma of control rats in vivo. The rat plasma exosomes could be taken up by H9c2 cells. In addition, miR-24 was present in RIPC-induced exosomes and played a role in reducing oxidative stress-mediated injury and decreasing apoptosis by downregulating Bim expression in H2O2-treated H9c2 cells in vitro. In vivo, miR-24 in RIPC-induced exosomes reduced cardiomyocyte apoptosis, attenuated the infarct size and improved heart function. Furthermore, the apoptosis-reducing effect of miR-24 was counteracted by miR-24 antagomirs or inhibitors both in vitro and in vivo. Therefore, we provided evidence that RIPC-induced exosomes could reduce apoptosis by transferring miR-24 in a paracrine manner and that miR-24 in the exosomes plays a central role in mediating the protective effects of RIPC.