Exosomes from MiR-126-Overexpressing Adscs Are Therapeutic in Relieving Acute Myocardial Ischaemic Injury
Exosomes from MiR-126-Overexpressing Adscs Are Therapeutic in Relieving Acute Myocardial Ischaemic Injury
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来自miR-126过表达的Adscs的Exosomes在缓解急性心肌缺血损伤中的治疗作用
DOI：
10.1159/000485949
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发表时间：
2017-01-01
影响因子：
--
通讯作者：
Jin, Mingming
中科院分区：
文献类型：
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作者：
Luo, Qiancheng;Guo, Dongfeng;Jin, Mingming
背景/目标：最近的研究表明，外泌体在脂肪干细胞移植介导的缺血性心脏病治疗中发挥重要作用。但治疗效果并不明显。本研究的目的是研究富含microRNA（miR）-126的ADSC衍生的外泌体是否对急性心肌梗死（AMI）具有更好的保护作用。研究方法：通过透射电子显微镜表征外泌体，并使用纳米颗粒跟踪分析进一步检查外泌体颗粒。建立大鼠心肌梗死模型和体外缺氧诱导H9 c2心肌细胞损伤模型，研究miR-126过表达的ADSCs中exosomes的保护机制。结果如下：体外实验结果表明，来源于miR-126过表达的ADSC的外泌体通过减少缺氧诱导过程中炎症因子的表达来减少H9 c2心肌细胞损伤。富含miR-126的外泌体还降低了缺氧条件下H9 c2细胞纤维化相关蛋白的表达。Matrigel（R）和Transwell（R）测定显示，富含miR-126的外泌体分别显著促进微血管生成和迁移。体内研究证实，来源于ADSC的外泌体显著减少了梗死的心肌损伤面积，尤其是在富含miR-126的外泌体治疗后。在用富含miR-126的外泌体治疗后，心脏纤维化和炎性细胞因子表达也降低。而在AMI大鼠梗死区，血管生成明显促进。结论：结果表明，miR-126增强的ADSC衍生的外泌体的表达通过保护心肌细胞免于凋亡、炎症、纤维化和增加的血管生成来防止心肌损伤。(C)2017作者（S）由S发布。Karger AG，巴塞尔。
Background/Aims: Recent studies have indicated that exosomes play an important role in adipose-derived stem cell (ADSC) transplant-mediated ischaemic heart disease therapy. However, the treatment effect is not obvious. The aim of this study is to investigate whether ADSC-derived exosomes enriched with microRNA (miR)-126 have a more protective effect on acute myocardial infarction (AMI). Methods: Exosomes were characterized by transmission electron microscopy, and the exosome particles were further examined using nanoparticle tracking analyses. A rat model of myocardial infarction and in vitro model of hypoxia-induced H9c2 myocardial cell injury were established to study the protective mechanism of exosomes from miR-126-overexpressing ADSCs. Results: The in vitro results showed that exosomes derived from miR-126-overexpressing ADSCs decreased H9c2 myocardial cell injury by reducing inflammation factor expression during hypoxia induction. The miR-126-enriched exosomes also decreased the expression of fibrosis-related proteins of H9c2 cells under hypoxic conditions. Matrigel (R) and Transwell (R) assays showed that miR-126-enriched exosomes significantly promoted microvascular generation and migration, respectively. In vivo studies confirmed that exosomes derived from ADSCs significantly decreased the myocardial injury area of infarction, especially after miR-126-enriched exosome treatment. Cardiac fibrosis and inflammatory cytokine expression were also decreased after treatment with miR-126-enriched exosomes. However, blood vessel formation was promoted in the infarction region of AMI rats. Conclusions: The results suggested that the expression of miR-126-enhanced ADSC-derived exosomes prevented myocardial damage by protecting myocardial cells from apoptosis, inflammation, fibrosis, and increased angiogenesis. (C) 2017 The Author(s). Published by S. Karger AG, Basel.