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.

These findings demonstrate that modification of the heparin-binding region of FGF1 significantly improves the cardioprotective efficacy, even in the presence of heparin, identifying a novel FGF ligand available for therapeutic use in ischemic heart disease.

Bim is a potent pro-apoptotic BH3-only Bcl-2 member. However, the expression of Bim and its role in cardiac injury induced by ischemia remain unclear. H9c2 cells were subjected to a glucose and oxygen-deprived (GOD) condition in vitro, mimicking ischemia environment in vivo. GOD treatment augmented the expression of Bim and induced the apoptosis of H9c2 cells. Silencing of Bim by RNAi significantly attenuated GOD-induced cytotoxicity, suppressed mitochondrial membrane potential △Ψm loss, inhibited caspase 3 activation and reduced apoptosis. The data demonstrate that Bim is upregulated by GOD in a time-dependent manner in H9c2 cells, and enhances mitochondrial apoptosis dependent on the activation of caspase 3. Silencing of Bim may be a promising therapeutic strategy in ischemia related heart diseases.

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Objectives To determine the effects of co-exposure to ischemia and cold stress on cardiac injury and whether Bim is involved in this situation. Methods Myocardial ischemia model was established by permanent ligation of left coronary artery. Sprague-Dawley rats were randomly divided to four groups (n=12): sham+normal temperature (S group); sham+cold stress (SC group);

Objective To investigate the role of atorvastatin in myocardium of rats following co-stress of myocardial ischemia and cold stress, and the relative mechanism. Methods Seventy male Sprague-Dawley rats were randomly divided to fi ve groups: sham+normal temperature (S group); sham+cold stress (SC group); myocardial ischemia+normal temperature (I group); myocardial ischemia+cold stress (IC group); atorvastatin treatment group (A group). Co-stress

ObjectiveThe purpose of this study was to investigate the potential cardioprotection roles of autophagy induced by ischemia/reperfusion (I/R) against apopotosis in cardiac myocytes, and tries to clarify the effects of PI3K in this process. Methods We employed simulated I/R of neonatal rat ventricular myocytes as an in vitro model of I/R injury to the heart. Cardiac myocytes were exposed to 3h hypoxia followed by 14h of reoxygenation, and during the reoxygenation cardiac myocytes were treated with 10mM 3-Methyladenine (3-MA) to inhibit autophagy or 50uM rapamycin to enhance autophagy. Then, we used real-time quantitative PCR (qPCR) to investigate the expression levels of Beclin 1, Bim, and caspase-3. Western blot analysis was used to examine variation in the expression of LC3-II/I (a marker of autophagy), Bim, caspase-3 and PI3K. Results Our results demonstrated that the mRNA expression of Beclin 1 and the ratio of LC3II/I were significantly increased when myocytes followed sI/R (simulated I/R). Moreover, autophagy enhanced by rapamycin during sI/R, significantly reduced the mRNA expression of Bim and caspase-3, and downregulation of the protein expression level of Bim, caspase-3 and PI3K. In contrast, the mRNA expression of Bim and caspase-3 was increased significantly, and the expression of Bim, caspase-3 and PI3K elevated when 3-MA inhibited the activation of autophagy. Conclusions Our results demonstrate that autophagy induced by sI/R constitutes a powerful and previously uncharacterized protective mechanism against apopotosis in cardiac myocytes via downregulating the pro-apopototic protein Bim and caspase-3, which is downregulated by PI3K. Rapamycin, the autophagic induction, can be used to reduced damage of fatal I/R injury via protecting against apoptosis, which may provide novel strategies for clinical treatment of I/R injury.