Cardiac progenitor-derived exosomes protect ischemic myocardium from acute ischemia/reperfusion injury.
Cardiac progenitor-derived exosomes protect ischemic myocardium from acute ischemia/reperfusion injury.
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DOI：
10.1016/j.bbrc.2013.01.015
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发表时间：
2013-02-15
影响因子：
3.1
通讯作者：
Tang, Yaoliang
中科院分区：
文献类型：
--
作者：
Chen, Lijuan;Wang, Yingjie;Pan, Yaohua;Zhang, Lan;Shen, Chengxing;Qin, Gangjian;Ashraf, Muhammad;Weintraub, Neal;Ma, Genshan;Tang, Yaoliang
心脏祖细胞（CPC）通过旁分泌效应介导心脏保护作用。迄今为止，大多数研究集中在分泌型旁分泌蛋白上。本文研究CPC衍生的exosomes对急性缺血/再灌注（MI/R）损伤心肌的保护作用。采用两步法从小鼠心脏中分离CPC。从条件培养基中纯化外泌体，并使用CD 63作为标记物通过电子显微照片和Western印迹进行确认。qRT-PCR显示CPC-外泌体具有高水平的GATA 4-响应性-miR-451表达。用PKH 26标记exosomes，观察到H9 C2心肌细胞在孵育12小时后可高效摄取exosomes。CPC-外泌体通过体外抑制caspase 3/7活化保护H9 C2免受氧化应激。与PBS对照相比，在急性小鼠心肌缺血/再灌注模型中CPC-外来体的体内递送抑制心肌细胞凋亡约53%（p<0.05）。我们的研究结果首次表明，CPC-外泌体可用作心脏保护的治疗载体，并突出了使用非细胞外泌体治疗心脏疾病的新视角。
Cardiac progenitors (CPC) mediate cardioprotection via paracrine effects. To date, most of studies focused on secreted paracrine proteins. Here we investigated the CPC-derived-exosomes on protecting myocardium from acute ischemia/reperfusion (MI/R) injury. CPC were isolated from mouse heart using two-step protocol. Exosomes were purified from conditional medium, and confirmed by electron micrograph and Western blot using CD63 as a marker. qRT-PCR shows that CPC- exosomes have high level expression of GATA4-responsive-miR-451. Exosomes were ex vivo labeled with PKH26, We observed exosomes can be uptaken by H9C2 cardiomyoblasts with high efficiency after 12 hours incubation. CPC-exosomes protect H9C2 from oxidative stress by inhibiting caspase 3/7 activation in vitro. In vivo delivery of CPC-exosomes in an acute mouse myocardial ischemia/reperfusion model inhibited cardiomyocyte apoptosis by about 53% in comparison with PBS control(p<0.05). Our results suggest, for the first time, the CPC-exosomes can be used as a therapeutic vehicle for cardioprotection, and highlights a new perspective for using non-cell exosomes for cardiac disease.
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影响因子：
6.1
作者：
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