Department of Geriatrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Mol Immunol. 2021 Aug;136:26-35. doi: 10.1016/j.molimm.2021.05.006. Epub 2021 May 28.
Emerging evidence has indicated that exosomes serve as key regulators in acute myocardial infarction (AMI). This study was determined to investigate the effect of M2 macrophage-derived exosomes (M2-Exos) in AMI and the further mechanism.
M2 macrophages were induced and M2-exos were isolated and verified. The AMI mouse model was prepared by ligation of the left anterior descending coronary artery (LAD) and then intravenously injected with the isolated M2-exos. The mouse cardiac function was assessed by echocardiography. Hematoxylin and eosin (HE) staining and TUNEL assay were conducted to examine myocardial lesion and apoptosis in cardiac tissues. The expressions of associated molecules were detected by quantitative real time-PCR (qRT-PCR) and western blot. MTT assay, Flow cytometry and Dual-luciferase reporter assay were carried out to detect cell viability, apoptosis and the interaction of miRNA and the target.
M2-Exos could promote cardiac repair in AMI mice. M2-Exos suppressed apoptosis and enhanced viability of hypoxia-induced cardiomyocytes through delivery of miR-1271-5p. SOX6 is a direct target of miR-1271-5p. miR-1271-5p decreased cardiomyocyte apoptosis induced by hypoxia and alleviated cardiac injury in AMI via down-regulating SOX6 expression.
We identified that M2-Exos could carry miR-1271-5p to reduce apoptosis of cardiomyocytes and promote cardiac repair via down-regulating SOX6.
新出现的证据表明，外泌体在急性心肌梗死（AMI）中充当关键调节因子。本研究旨在探讨 M2 巨噬细胞衍生的外泌体（M2-Exos）在 AMI 中的作用及其进一步的机制。
诱导 M2 巨噬细胞，分离并验证 M2-exos。结扎左前降支冠状动脉（LAD）制备 AMI 小鼠模型，然后静脉注射分离的 M2-exos。通过超声心动图评估小鼠心功能。通过苏木精和伊红（HE）染色和 TUNEL 检测评估心肌病变和心脏组织中的细胞凋亡。通过定量实时 PCR（qRT-PCR）和蛋白质印迹检测相关分子的表达。通过 MTT 检测、流式细胞术和双荧光素酶报告基因检测检测细胞活力、凋亡以及 miRNA 和靶标的相互作用。
M2-Exos 可促进 AMI 小鼠的心脏修复。M2-Exos 通过递送 miR-1271-5p 抑制缺氧诱导的心肌细胞凋亡并增强其活力。SOX6 是 miR-1271-5p 的直接靶标。miR-1271-5p 通过下调 SOX6 表达减少缺氧诱导的心肌细胞凋亡，并通过减轻 AMI 中的心脏损伤来改善心脏修复。
我们发现 M2-Exos 可以通过携带 miR-1271-5p 来减少心肌细胞凋亡并通过下调 SOX6 促进心脏修复。
