gw-4869 and Myocardial-Ischemia

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 miRNAs, 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

Topics: Aniline Compounds; Animals; Benzylidene Compounds; Cytokines; Disease Models, Animal; Extracellular Vesicles; Heart Injuries; Inflammation; Janus Kinase 2; Macrophages; Male; Mice; Mice, Inbred C57BL; MicroRNAs; Microscopy, Confocal; Myocardial Ischemia; Myocardial Reperfusion Injury; Signal Transduction; STAT1 Transcription Factor