Divisions of General Medicine, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan.
Graduate Institute of Adult Education, National Kaohsiung Normal University, Kaohsiung 802, Taiwan.
Cells. 2019 Aug 19;8(8):935. doi: 10.3390/cells8080935.
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.
缺血心肌来源的条件培养基可改善心肌梗死后啮齿动物的心脏功能。细胞间通讯的外泌体 miRNA 介导被认为介导了条件培养基对缺血损伤的保护作用。应用了氧葡萄糖剥夺 (OGD) 处理的心肌细胞和急性心肌梗死 (AMI) 的大鼠模型。分析了在缺血应激下心肌疾病相关 miRNA 在心肌细胞、心肌成纤维细胞、心室心肌和心肌细胞来源的条件培养基中的表达谱。应用原代细胞培养模型和心肌梗死大鼠模型来研究 miRNA 在调节心肌细胞凋亡、成纤维细胞激活、免疫细胞浸润和心肌梗死中的作用。结果表明，OGD 处理后，miR-21 在心肌细胞、心肌成纤维细胞和心肌细胞来源的条件培养基 (CM) 中的表达水平上调。miR-21 耗竭后，CM 对心肌细胞对抗氧化应激、增强成纤维细胞激活和促进内皮细胞血管生成的保护作用降低。CM 的给予减少了 AMI 大鼠心肌中的梗死面积和免疫细胞浸润，而 miR-21 的耗竭降低了 CM 的作用。总之，miR-21 在缺血性心肌细胞之间的细胞间通讯中起作用。miR-21 的表达对于条件培养基对抗心肌梗死的保护作用很重要。
