MicroRNA-21 Mediates the Protective Effect of Cardiomyocyte-Derived Conditioned Medium on Ameliorating Myocardial Infarction in Rats

Cells - Tập 8 Số 8 - Trang 935
Chih‐Hung Chen1,2, Shu-Yuan Hsu3,4, Chien‐Chih Chiu5, Steve Leu5,4
1Divisions of General Medicine, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan
2Graduate Institute of Adult Education, National Kaohsiung Normal University, Kaohsiung 802, Taiwan
3Department of Anatomy, Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
4Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan
5Department of Biotechnology, College of Life Science, Kaohsiung Medical University, Kaohsiung 807, Taiwan

Tóm tắt

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.

Từ khóa


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