Mesenchymal stem cell-derived exosomes regulate cardiomyocyte autophagy and cardiac function via microRNA-21-5p in rats with myocardial ischemia
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Department of Cardiovascular Medicine,Fifth Affiliated Hospital of Xinjiang Medical University, Urumqi 830011, China

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R-33

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    Abstract:

    Objective To investigate whether exosomes (Exos) secreted by mesenchymal stem cells (MSCs) regulate cardiac autophagy and cardiac function in rats with myocardial ischemia through miR-21-5p. Methods In vitro,the effect of MSC exos on H2O2 stimulated H9C2 cells was observed. Cell viability was detected by the CCK- 8 assay, apoptosis was detected by flow cytometry, reactive oxygen species ( ROS ) production was analyzed by fluorescence microscopy, and autophagy-related proteins and autophagy formation were detected by immunoblotting and fluorescent GFP- LC3. In rat model of myocardial ischemia-reperfusion injury ( MI/ IR), the effects of MSC exos on cell apoptosis, myocardial LC3b expression, and cardiac function were examined by TUNEL assay, immunohistochemistry, and echocardiography. Results In vitro, MSC-Exos significantly increased the activity of H9C2s stimulated by H2O2(P<0. 05) and decreased the production of ROS and the rate of apoptosis (P<0. 05). Compared with the H2O2+MSCs-Exos group, the cell viability in the H2O2+MSC-ExossimiR-21-5p group was significantly decreased (P<0. 01), whereas ROS production and apoptosis were significantly increased (P<0. 01). Western blot analysis showed that compared with the H2O2 group, the expression of LC3B-Ⅱ/ LC3B-I and LC3B-II in the H2O2+MSC-ExossimiR-21-5p group was significantly lower than that in the H2O2+MSCs-Exos group (P<0. 05), while the expression of p62 was significantly increased (P<0. 05). Autophagy flux result : Compared with the H2O2 group, GFP-LC3 was increased in the H2O2+ MSCs-Exos group. Furthermore, Compared with the H2O2+ MSCs-Exos group, the number of GFP-LC3 points in the cells of the H2O2+ MSC-ExossimiR-21-5p group was significantly reduced (P<0. 05). in vivo, RT-qPCR analysis showed that there was a positive correlation between the expression of miR-21-5p in MSCs-Exos and MI/ RI. Compared with other groups, the expression of LC3B in the MI/ RI+ MSCs-Exos group was significantly increased (P<0. 01), myocardial apoptosis was significantly reduced (P<0. 01), and the fraction shortening rate (%FS) and left ventricular ejection fraction (LVEF) were significantly increased (P<0. 05). Conclusions MSCs-Exos can improve cardiac function in MI/ RI rats by regulating myocardial autophagy, and its mechanism may be related to miR-21-5p transfer.

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History
  • Received:November 11,2019
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  • Online: June 19,2020
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