Myocardial ischemia-reperfusion induced cardiac extracellular vesicles harbour proinflammatory features and aggravate heart injury

被引:99
作者
Ge, Xinyu [1 ,2 ,3 ,4 ]
Meng, Qingshu [1 ,2 ,3 ]
Wei, Lu [1 ,2 ,3 ]
Liu, Jing [1 ,2 ,3 ,4 ]
Li, Mimi [1 ,2 ,3 ]
Liang, Xiaoting [1 ,2 ,3 ]
Lin, Fang [1 ,2 ,3 ]
Zhang, Yuhui [7 ]
Li, Yinzhen [1 ,6 ]
Liu, Zhongmin [1 ,2 ,3 ,4 ,5 ]
Fan, Huimin [2 ,3 ,4 ,5 ]
Zhou, Xiaohui [1 ,2 ,3 ]
机构
[1] Tongji Univ, Shanghai East Hosp, Res Ctr Translat Med, Sch Med, Shanghai, Peoples R China
[2] Tongji Univ, Shanghai East Hosp, Shanghai Heart Failure Res Ctr, Sch Med, Shanghai, Peoples R China
[3] Tongji Univ, Inst Integrated Tradit Chinese & Western Med Card, Sch Med, Shanghai, Peoples R China
[4] Tongji Univ, Shanghai East Hosp, Dept Cardiothorac Surg, Sch Med, Shanghai, Peoples R China
[5] Tongji Univ, Shanghai East Hosp, Dept Heart Failure, Sch Med, Shanghai, Peoples R China
[6] Tongji Univ, Shanghai East Hosp, Sch Med, Dept Resp Med, Shanghai, Peoples R China
[7] Tongji Univ, Shanghai East Hosp, Sch Med, Dept Ultrasound, Shanghai, Peoples R China
关键词
extracellular vesicles; heart injury; inflammation; ischemia-reperfusion injury; macrophage polarization; miRNAs; NEUTROPHIL RECRUITMENT; CELL; INFLAMMATION; MICRORNAS; EXOSOMES; DISEASE; MIRNAS; CXCL2; MECHANISMS; INHIBITION;
D O I
10.1002/jev2.12072
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Extracellular vesicles (EVs) curb important biological functions. We previously disclosed that ischemia-reperfusion (IR) induces increased release of EVs (IR-EVs) in the heart. However, the role of IR-EVs in IR pathological process remains poorly understood. Here we found that adoptive transfer of IR-EVs aggravated IR induced heart injury, and EV inhibition by GW4869 reduced the IR injury. Our in vivo and in vitro investigations substantiated that IR-EVs facilitated M1-like polarization of macrophages with increased expression of proinflammatory cytokines. Further, we disclosed the miRNA profile in cardiac EVs and confirmed the enrichment of miR-NAs, such as miR-155-5p in IR-EVs compared to EVs from the sham heart (S-EVs). In particular, IR-EVs transferred miR-155-5p to macrophages and enhanced the inflammatory response through activating JAK2/STAT1 pathway. Interestingly, IR-EVs not only boosted the local inflammation in the heart, but even triggered systemic inflammation in distant organs. Taken together, we newly identify an IR-EVs-miR-155-5p-M1 polarization axis in the heart post IR. The EVs derived from IR-injured heart contribute to both local and systemic inflammation. Importantly, EV inhibition by GW4869 is supposed to be a promising therapeutic strategy for IR injury.
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页数:17
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