4.5 Article

Circulating exosomes repair endothelial cell damage by delivering miR-193a-5p

期刊

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
卷 25, 期 4, 页码 2176-2189

出版社

WILEY
DOI: 10.1111/jcmm.16202

关键词

exosomes; microRNAs; oxidative damage

资金

  1. National Natural Science Foundation of China [81800267, 81870328]
  2. Henan Medical Science and Technology Joint Building Program [2018020002]
  3. Henan Thousand Talents Program [ZYQR201912131]
  4. Henan Province Youth Talent Promoting Project [2020HYTP051]
  5. Excellent Youth Science Foundation of Henan Province

向作者/读者索取更多资源

Circulating exosomes shuttle between cells via dynamin and deliver miR-193a-5p to protect endothelial cells from oxidative stress damage via ACVR1, indicating a potential therapeutic target for cardiovascular diseases.
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.

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