Atorvastatin-pretreated mesenchymal stem cell-derived extracellular vesicles promote cardiac repair after myocardial infarction via shifting macrophage polarization by targeting microRNA-139-3p/Stat1 pathway

Autor: Yu Ning, Peisen Huang, Guihao Chen, Yuyan Xiong, Zhaoting Gong, Chunxiao Wu, Junyan Xu, Wenyang Jiang, Xiaosong Li, Ruijie Tang, Lili Zhang, Mengjin Hu, Jing Xu, Jun Xu, Haiyan Qian, Chen Jin, Yuejin Yang
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: BMC Medicine, Vol 21, Iss 1, Pp 1-18 (2023)
Druh dokumentu: article
ISSN: 1741-7015
DOI: 10.1186/s12916-023-02778-x
Popis: Abstract Background Extracellular vesicles (EVs) derived from bone marrow mesenchymal stem cells (MSCs) pretreated with atorvastatin (ATV) (MSCATV-EV) have a superior cardiac repair effect on acute myocardial infarction (AMI). The mechanisms, however, have not been fully elucidated. This study aims to explore whether inflammation alleviation of infarct region via macrophage polarization plays a key role in the efficacy of MSCATV-EV. Methods MSCATV-EV or MSC-EV were intramyocardially injected 30 min after coronary ligation in AMI rats. Macrophage infiltration and polarization (day 3), cardiac function (days 0, 3, 7, 28), and infarct size (day 28) were measured. EV small RNA sequencing and bioinformatics analysis were conducted for differentially expressed miRNAs between MSCATV-EV and MSC-EV. Macrophages were isolated from rat bone marrow for molecular mechanism analysis. miRNA mimics or inhibitors were transfected into EVs or macrophages to analyze its effects on macrophage polarization and cardiac repair in vitro and in vivo. Results MSCATV-EV significantly reduced the amount of CD68+ total macrophages and increased CD206+ M2 macrophages of infarct zone on day 3 after AMI compared with MSC-EV group (P
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