Plasma exosomes induced by remote ischaemic preconditioning attenuate myocardial ischaemia/reperfusion injury by transferring miR-24

Abstract

Remote ischaemic preconditioning (RIPC) is well known to protect the myocardium against ischaemia/reperfusion injury (IRI). Exosomes are small extracellular vesicles that have become the key mediators of intercellular communication. Various studies have confirmed that circulating exosomes mediate RIPC. However, the underlying mechanisms for RIPC-induced exosome-mediated cardioprotection remain elusive. In our study, we found that the expression level of miR-24 was higher in exosomes derived from the plasma of rats subjected to RIPC than in exosomes derived from the plasma of control rats in vivo. The rat plasma exosomes could be taken up by H9c2 cells. In addition, miR-24 was present in RIPC-induced exosomes and played a role in reducing oxidative stress-mediated injury and decreasing apoptosis by downregulating Bim expression in H2O2-treated H9c2 cells in vitro. In vivo, miR-24 in RIPC-induced exosomes reduced cardiomyocyte apoptosis, attenuated the infarct size and improved heart function. Furthermore, the apoptosis-reducing effect of miR-24 was counteracted by miR-24 antagomirs or inhibitors both in vitro and in vivo. Therefore, we provided evidence that RIPC-induced exosomes could reduce apoptosis by transferring miR-24 in a paracrine manner and that miR-24 in the exosomes plays a central role in mediating the protective effects of RIPC.

Emerging role of non-coding RNAs and extracellular vesicles in cardioprotection by remote ischemic conditioning of the heart

“…Finally, the anti-apoptotic effect of miR-24 was counteracted by miR-24 antagomiRs or inhibitors both in vitro and in vivo suggesting that RIPC-induced exosomes could reduce apoptosis by paracrine transfer of miR-24. This further supports that exosomal miRNA-24 plays an important role in mediating the protective effects of RIPC (Minghua et al, 2018). The important role of miRNA cargo of extracellular vesicles in cardioprotection by RIPC has been supported by recently published human studies in coronary artery bypass (CABG) patients.…”

“…Recently, extracellular vesicles, particularly exosomes, have been identified as potential carriers of cardioprotective signals of RIC (Giricz et al, 2014;Minghua et al, 2018). In line with these findings, the main goal of the current review is to summarize the most recent knowledge about the potential involvement of extracellular vesicles in remote cardioprotection.…”

“…It should be also pointed out that several miRNAs including miR-22 (Feng et al, 2014), miR-29a (Yamaguchi et al, 2015), and miR-24 (Minghua et al, 2018) have been proposed to be transferred in the cargo of extracellular vesicles and potentially exert cardioprotective effects in the target organ/heart. Potential involvement of miRNAs in RIPC-induced cardioprotection including those carried in extracellular vesicles is summarized in Fig.…”

Small extracellular vesicles from rat plasma promote migration and proliferation of vascular smooth muscle cells

“…1). No other groups so far have reported the concentration of plasma sEV from WKY and SHR, while the concentration of plasma sEV in Sprague-Dawley [22,35,37,46], Wistar [6], and Fisher 344 [9] rats was reported to be ranging between 10 8 -10 12 particles/ml. Therefore, the concentration of our sEV would be within the reasonable ranges and also was enough for the following analyses.…”

Extracellular micro/nanovesicles rescue kidney from ischemia‐reperfusion injury

“…Therefore, infusion of ECFC-EVs ameliorates renal IRI via transfer of miRNA-486-5p targeting PTEN (Viñas et al, 2016). An accumulating body of evidence has suggested that mitochondrial dynamics play an ExoQuick precipitation solution 10 µg Minghua et al (2018) important role in IRI (Calo, Dong, Kumar, Przyklenk, & Sanderson, 2013). Mitochondria are a class of dynamic subcellular entities that constantly experience fission and fusion.…”