From cerebral ischemia towards myocardial, renal, and hepatic ischemia: Exosomal miRNAs as a general concept of intercellular communication in ischemia-reperfusion injury.

Ischemia-reperfusion injury occurs when blood supply to an organ is disrupted-ischemia-and then restored-reperfusion-and is commonly found under different pathological settings such as cerebral, myocardial, renal, and hepatic ischemia-reperfusion injuries. Despite apparent differences as to the cause of these diseases, emerging evidence suggests that common signaling pathways, such as exosomes and microRNAs (miRNAs), are involved in this context. Although miRNAs are also found in the extracellular milieu, plenty of miRNAs are found in exosomes and are thus protected from degradation. miRNAs selectively sorted into exosomes potentially regulate specific aspects of the onset and progression of ischemic stroke. Such mechanisms involve the regulation of cell survival, inflammation, angiogenesis, and neurogenesis. Likewise, miRNAs shuttled into exosomes are involved in the pathogenesis of myocardial, renal, and hepatic ischemia-reperfusion injuries. This review will discuss recent evidence on the exosome-facilitated progression of four ischemia-reperfusion conditions, particularly concerning miRNAs within these vesicles. The notion is given to miRNAs participating in more than one of the four conditions, indicating a considerable degree of overlap across ischemia-reperfusion conditions. We will conclude the review by highlighting clinical opportunities of such exosome-derived miRNAs both as biomarkers and as therapeutic targets.