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Circulating exosomes repair endothelial cell damage by delivering miR-193a-5p |
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| Authors: | Chang Cao Bo Wang Junnan Tang Jimin Zhao Jiacheng Guo Qianqian Guo Xiaoting Yue Zenglei Zhang Gangqiong Liu Hui Zhang Yunzhe Wang Jinying Zhang |
| Affiliation: | 1. Department of Cardiology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China Key Laboratory of Cardiac Injury and Repair of Henan Province, Zhengzhou, Henan, China Contribution: Conceptualization (equal), Data curation (equal), Formal analysis (equal), Investigation (equal), Methodology (equal), Writing - original draft (equal);2. Department of Cardiology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China Key Laboratory of Cardiac Injury and Repair of Henan Province, Zhengzhou, Henan, China Contribution: Data curation (equal), Formal analysis (equal), Investigation (equal), Methodology (equal), Writing - original draft (equal);3. Department of Cardiology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China;4. Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China Contribution: Investigation (equal), Methodology (equal), Visualization (equal);5. Department of Cardiology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China Key Laboratory of Cardiac Injury and Repair of Henan Province, Zhengzhou, Henan, China Contribution: Investigation (equal), Methodology (equal);6. Department of Cardiology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China Key Laboratory of Cardiac Injury and Repair of Henan Province, Zhengzhou, Henan, China Contribution: Formal analysis (equal), Investigation (equal);7. Department of Cardiology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China Key Laboratory of Cardiac Injury and Repair of Henan Province, Zhengzhou, Henan, China Contribution: Investigation (equal), Visualization (equal);8. Department of Cardiology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China Key Laboratory of Cardiac Injury and Repair of Henan Province, Zhengzhou, Henan, China Contribution: Formal analysis (equal);9. Department of Cardiology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China Contribution: Formal analysis (equal);10. Department of Cardiology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China Contribution: Investigation (equal), Methodology (equal) |
| Abstract: | Circulating exosomes delivering microRNAs are involved in the occurrence and development of cardiovascular diseases. How are the circulating exosomes involved in the repair of endothelial injury in acute myocardial infarction (AMI) convalescence (3-7 days) was still not clear. In this study, circulating exosomes from AMI patients (AMI-Exo) and healthy controls (Normal-Exo) were extracted. In vitro and in vivo, our study showed that circulating exosomes protected endothelial cells (HUVECs) from oxidative stress damage; meanwhile, Normal-Exo showed better protective effects. Through the application of related inhibitors, we found that circulating exosomes shuttled between HUVECs via dynamin. Microarry analysis and qRT-PCR of circulating exosomes showed higher expression of miR-193a-5p in Normal-Exo. Our study showed that miR-193a-5p was the key factor on protecting endothelial cells in vitro and in vivo. Bioinformatics analyses found that activin A receptor type I (ACVR1) was the potential downstream target of miR-193a-5p, which was confirmed by ACVR1 expression and dual-luciferase report. Inhibitor of ACVR1 showed similar protective effects as miR-193a-5p. While overexpression of ACVR1 could attenuate protective effects of miR-193a-5p. To sum up, these findings suggest that circulating exosomes could shuttle between cells through dynamin and deliver miR-193a-5p to protect endothelial cells from oxidative stress damage via ACVR1. |
| Keywords: | exosomes microRNAs oxidative damage |