MicroRNA-21 Mediates the Protective Effect of Cardiomyocyte-Derived Conditioned Medium on Ameliorating Myocardial Infarction in Rats
MicroRNA-21 Mediates the Protective Effect of Cardiomyocyte-Derived Conditioned Medium on Ameliorating Myocardial Infarction in Rats
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DOI：
10.3390/cells8080935
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发表时间：
2019-08-01
期刊：
影响因子：
6
通讯作者：
Leu, Steve
中科院分区：
文献类型：
--
作者：
Chen, Chih-Hung;Hsu, Shu-Yuan;Leu, Steve
缺血心肌条件培养液改善心肌梗死后大鼠心功能。外泌体miRNA介导的细胞间通讯被认为介导了条件培养基对缺血性损伤的保护作用。应用氧糖剥夺（OGD）处理的心肌细胞和急性心肌梗死（AMI）大鼠模型。分析心肌疾病相关miRNAs在心肌细胞、心脏成纤维细胞、心室肌和缺血应激下心肌细胞条件培养液中的表达谱。采用原代培养细胞模型和大鼠心肌梗死模型，研究miRNA在心肌细胞凋亡、成纤维细胞活化、免疫细胞浸润和心肌梗死中的作用。结果显示，心肌细胞、心脏成纤维细胞和心肌细胞来源的条件培养基（CM）中的miR-21表达水平随着OGD处理而上调。随着miR-21的缺失，CM对心肌细胞抗氧化应激、增强成纤维细胞活化和促进内皮细胞血管生成的保护作用降低。给予CM可减少AMI大鼠心肌梗死面积和免疫细胞浸润，而去除miR-21则可降低CM的作用。总之，miR-21在缺血心肌细胞间的细胞间通讯中发挥作用。miR-21的表达在条件培养液对心肌梗死的保护作用中起重要作用。
Conditioned medium derived from ischemic myocardium improves rodent cardiac function after myocardial infarction. Exosomal miRNA-mediated intercellular communication is considered to mediate the protective effect of conditioned medium against ischemic injury. Oxygen-glucose-deprivation (OGD)-treated cardiac cells and a rat model with acute myocardial infarction (AMI) were applied. The expression profiles of myocardial-disease-associated miRNAs in cardiomyocytes, cardiac fibroblasts, ventricular myocardium, and conditioned medium derived from cardiomyocytes under ischemic stresses were analyzed. Primary cultured cell model and a rat model with myocardial infarction were applied to examine the role of miRNA in regulating cardiomyocyte apoptosis, fibroblast activation, immune cell infiltration, and myocardial infarction. Results showed that expression levels of miR-21 in cardiomyocytes, cardiac fibroblasts, and conditioned medium (CM) derived from cardiomyocytes were up-regulated with OGD treatment. With the depletion of miR-21, the protective effect of CM on cardiomyocytes against oxidative stress, enhanced fibroblast activation, and promotion of angiogenesis in endothelial cells were reduced. Administration of CM reduced the infarcted size and immune cell infiltration in myocardium of rats with AMI, while depletion of miR-21 reduced the effect of CM. In conclusion, miR-21 plays a role in intercellular communication among ischemic cardiac cells. The expression of miR-21 is important for the protective effect of conditioned medium against myocardial infarction.