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

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 (OG...

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Main Authors: Chih-Hung Chen, Shu-Yuan Hsu, Chien-Chih Chiu, Steve Leu
Format: Article
Language:English
Published: MDPI AG 2019-08-01
Series:Cells
Subjects:
Online Access:https://www.mdpi.com/2073-4409/8/8/935
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author Chih-Hung Chen
Shu-Yuan Hsu
Chien-Chih Chiu
Steve Leu
author_facet Chih-Hung Chen
Shu-Yuan Hsu
Chien-Chih Chiu
Steve Leu
author_sort Chih-Hung Chen
collection DOAJ
description 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.
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spelling doaj.art-20b5e780ce4746cf83171c2e993c4fc02023-09-02T21:57:04ZengMDPI AGCells2073-44092019-08-018893510.3390/cells8080935cells8080935MicroRNA-21 Mediates the Protective Effect of Cardiomyocyte-Derived Conditioned Medium on Ameliorating Myocardial Infarction in RatsChih-Hung Chen0Shu-Yuan Hsu1Chien-Chih Chiu2Steve Leu3Divisions of General Medicine, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, TaiwanInstitute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, TaiwanDepartment of Biotechnology, College of Life Science, Kaohsiung Medical University, Kaohsiung 807, TaiwanInstitute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, TaiwanConditioned 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.https://www.mdpi.com/2073-4409/8/8/935conditioned mediumoxygen-glucose-deprivationmicroRNA-21cardiomyocyte
spellingShingle Chih-Hung Chen
Shu-Yuan Hsu
Chien-Chih Chiu
Steve Leu
MicroRNA-21 Mediates the Protective Effect of Cardiomyocyte-Derived Conditioned Medium on Ameliorating Myocardial Infarction in Rats
Cells
conditioned medium
oxygen-glucose-deprivation
microRNA-21
cardiomyocyte
title MicroRNA-21 Mediates the Protective Effect of Cardiomyocyte-Derived Conditioned Medium on Ameliorating Myocardial Infarction in Rats
title_full MicroRNA-21 Mediates the Protective Effect of Cardiomyocyte-Derived Conditioned Medium on Ameliorating Myocardial Infarction in Rats
title_fullStr MicroRNA-21 Mediates the Protective Effect of Cardiomyocyte-Derived Conditioned Medium on Ameliorating Myocardial Infarction in Rats
title_full_unstemmed MicroRNA-21 Mediates the Protective Effect of Cardiomyocyte-Derived Conditioned Medium on Ameliorating Myocardial Infarction in Rats
title_short MicroRNA-21 Mediates the Protective Effect of Cardiomyocyte-Derived Conditioned Medium on Ameliorating Myocardial Infarction in Rats
title_sort microrna 21 mediates the protective effect of cardiomyocyte derived conditioned medium on ameliorating myocardial infarction in rats
topic conditioned medium
oxygen-glucose-deprivation
microRNA-21
cardiomyocyte
url https://www.mdpi.com/2073-4409/8/8/935
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AT shuyuanhsu microrna21mediatestheprotectiveeffectofcardiomyocytederivedconditionedmediumonamelioratingmyocardialinfarctioninrats
AT chienchihchiu microrna21mediatestheprotectiveeffectofcardiomyocytederivedconditionedmediumonamelioratingmyocardialinfarctioninrats
AT steveleu microrna21mediatestheprotectiveeffectofcardiomyocytederivedconditionedmediumonamelioratingmyocardialinfarctioninrats