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Here we found that adoptive transfer of IR\u2010EVs aggravated IR induced heart injury, and EV inhibition by GW4869 reduced the IR injury. Our in vivo and in vitro investigations substantiated that IR\u2010EVs facilitated M1\u2010like polarization of macrophages with increased expression of proinflammatory cytokines. Further, we disclosed the miRNA profile in cardiac EVs and confirmed the enrichment of miRNAs, such as miR\u2010155\u20105p in IR\u2010EVs compared to EVs from the sham heart (S\u2010EVs). In particular, IR\u2010EVs transferred miR\u2010155\u20105p to macrophages and enhanced the inflammatory response through activating JAK2\/STAT1 pathway. Interestingly, IR\u2010EVs not only boosted the local inflammation in the heart, but even triggered systemic inflammation in distant organs. Taken together, we newly identify an IR\u2010EVs\u2013miR\u2010155\u20105p<jats:bold>\u2013<\/jats:bold>M1 polarization axis in the heart post IR. The EVs derived from IR\u2010injured heart contribute to both local and systemic inflammation. Importantly, EV inhibition by GW4869 is supposed to be a promising therapeutic strategy for IR injury.<\/jats:p>","DOI":"10.1002\/jev2.12072","type":"journal-article","created":{"date-parts":[[2021,2,23]],"date-time":"2021-02-23T23:18:35Z","timestamp":1614122315000},"source":"Crossref","is-referenced-by-count":139,"title":["Myocardial ischemia\u2010reperfusion induced cardiac extracellular vesicles harbour proinflammatory features and aggravate heart injury"],"prefix":"10.1002","volume":"10","author":[{"given":"Xinyu","family":"Ge","sequence":"first","affiliation":[{"name":"Research Center for Translational Medicine Shanghai East Hospital Tongji University School of Medicine  Shanghai P.R. China"},{"name":"Shanghai Heart Failure Research Center Shanghai East Hospital Tongji University School of Medicine  Shanghai P.R. 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