Myocardial infarction (MI) is recognized as a major cause of death and disability around the world. Macrophage-derived extracellular vesicles (EVs) have been reportedly involved in the regulation of cellular responses to MI. Thus, we sought to clarify the mechanism by which macrophage-derived EVs regulate this process. RT-qPCR was carried out to determine miR-150 expression in an MI mouse model with ligation of the left anterior descending coronary artery (LAD) and in hypoxia/reoxygenation (H/R)-exposed cardiomyocytes. Bioinformatics analysis and dual luciferase reporter gene assay were adopted to identify the correlation of miR-150 with TP53 expression in cardiomyocytes. Gain- and loss-of function experiments were conducted in H/R-induced cardiomyocytes, cardiomyocytes incubated with EVs from miR-150 mimic-transfected macrophages, or MI-model mice treated with EVs from miR-150 mimic-transfected macrophages. HE and TUNEL staining assays were used for detecting inflammatory infiltration and cell apoptosis. The release of LDH by dead cardiomyocytes was measured with an LDH kit, and the apoptosis-related proteins, Bax, and cleaved-caspase 3 were determined by Western blot analysis. miR-150 expression was downregulated in the infarcted cardiac tissues of MI mice. Macrophage-derived EVs could transfer miR-150 into cardiomyocytes, where it directly targeted and suppressed TP53. Furthermore, miR-150 suppressed PTEN and activated p-AKT to upregulate IGF-1 expression. Furthermore, increased expression of EV-derived miR-150 prevented cardiomyocyte apoptosis in vitro, as evidenced by downregulated Bax and cleaved-caspase 3 and upregulated Bcl2 and alleviated MI in vivo. In conclusion, our study demonstrates the cardioprotective effect of macrophage-derived EV-miR-150 on MI-induced heart injury through negatively regulating the TP53-IGF-1 signaling pathway.

中文翻译：

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巨噬细胞释放的富含miR-150的细胞外囊泡可调节TP53-IGF-1轴以减轻心肌梗塞

心肌梗塞（MI）是世界范围内导致死亡和残疾的主要原因。据报道，巨噬细胞源性细胞外囊泡（EV）参与了对MI的细胞反应的调节。因此，我们试图阐明巨噬细胞源电动汽车调节这一过程的机制。进行RT-qPCR以确定MI小鼠模型中左前降支冠状动脉（LAD）结扎和缺氧/复氧（H / R）暴露的心肌细胞中miR-150的表达。采用生物信息学分析和双重荧光素酶报告基因检测方法鉴定miR-150与心肌细胞中TP53表达的相关性。功能获得和功能丧失实验是在H / R诱导的心肌细胞中进行的，心肌细胞与miR-150模拟转染的巨噬细胞的EV孵育，miR-150模拟转染的巨噬细胞的EV处理的MI或MI模型小鼠。HE和TUNEL染色测定法用于检测炎性浸润和细胞凋亡。用LDH试剂盒测定死亡的心肌细胞释放的LDH，并通过Western印迹分析测定凋亡相关蛋白Bax和裂解的半胱天冬酶3。在MI小鼠的梗塞心脏组织中，miR-150表达下调。巨噬细胞源电动汽车可以将miR-150转移到心肌细胞中，直接靶向并抑制TP53。此外，miR-150抑制PTEN并激活p-AKT以上调IGF-1表达。此外，EV衍生的miR-150的表达增加在体外阻止了心肌细胞凋亡，体内Bax和Caspase 3裂解，Bcl2上调和MI降低证明了这一点。结论，