Bone marrow mesenchymal stem cell‑derived exosomes protect against myocardial infarction by promoting autophagy

Zou,Liyuan; Ma,Xiaokun; Lin,Shuo; Wu,Bingyuan; Chen,Yang; Peng,Chaoquan

doi:10.3892/etm.2019.7874

Bone marrow mesenchymal stem cell‑derived exosomes protect against myocardial infarction by promoting autophagy

Authors:
- Liyuan Zou
- Xiaokun Ma
- Shuo Lin
- Bingyuan Wu
- Yang Chen
- Chaoquan Peng
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Affiliations: Department of Prevention and Health Care, The Third Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510630, P.R. China, Department of Medical Oncology, The Third Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510630, P.R. China, Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510630, P.R. China, Department of Cardiology, The Third Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510630, P.R. China
Published online on: August 9, 2019 https://doi.org/10.3892/etm.2019.7874
Pages: 2574-2582
Copyright: © Zou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Exosomes have been demonstrated to be effective in the treatment of a variety of cardiac disorders. However, the effects of mesenchymal stem cell (MSC) exosomes on myocardial infarction is yet to be determined. The current study aimed to investigate the potential therapeutic effects of MSC exosomes on myocardial injuries that are caused by myocardial infarction. MSCs were isolated from rat bone marrow and were used for exosome enrichment using culture medium. Confirmation that MSCs and exosomes had been successfully extracted was performed using flow cytometry, electron microscopy and western blot analysis. A rat myocardial ischemia reperfusion (I/R) model was established by ligation of the left anterior descending coronary artery. Rat myocardial injuries were determined using 2,3,5‑triphenyltetrazolium chloride, Masson and TUNEL staining. H9c2 cell proliferation, apoptosis and migration were analyzed using 5‑ethynyl‑2'‑deoxyuridine, Hoechst staining, flow cytometry and Transwell assays. Marker gene expression was evaluated using reverse transcription‑quantitative PCR, western blot analysis and immunofluorescence. Rat MSC exosomes were revealed to suppress myocardial injury and the myocardiocyte functions that were induced by I/R. The results also demonstrated decreased apoptotic protease activating factor‑1 and increased autophagy‑related protein 13 expression. The H9c2 cell proliferation and migration inhibition, as well as cell apoptosis during hypoxia‑reoxygenation (H/R), were suppressed by rat MSC exosomes, with an alteration of the expression of apoptotic and autophagic genes also being demonstrated. The application of autophagy inhibitor 3‑methyladenine significantly mitigated the effect of exosomes on H9c2 cell proliferation and apoptosis, which were induced by H/R. Rat MSC exosomes inhibited myocardial infarction pathogenesis, possibly by regulating autophagy.

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