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Inhibiting miR-155 protects against myocardial ischemia/reperfusion injury via targeted regulation of HIF-1α in rats

OBJECTIVE(S): The aim of this study was to identify the role of miR-155 in the myocardial ischemia/reperfusion (I/R) injury through targeting hypoxia-inducible factor 1-alpha (HIF-1α). MATERIALS AND METHODS: We constructed rat models with myocardial I/R injury and H9C2 cell models with hypoxia/reoxy...

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Autores principales: Chen, Jian-Guo, Xu, Xiao-Ming, Ji, Hui, Sun, Bo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Mashhad University of Medical Sciences 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6880526/
https://www.ncbi.nlm.nih.gov/pubmed/31807249
http://dx.doi.org/10.22038/ijbms.2019.34853.8270
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author Chen, Jian-Guo
Xu, Xiao-Ming
Ji, Hui
Sun, Bo
author_facet Chen, Jian-Guo
Xu, Xiao-Ming
Ji, Hui
Sun, Bo
author_sort Chen, Jian-Guo
collection PubMed
description OBJECTIVE(S): The aim of this study was to identify the role of miR-155 in the myocardial ischemia/reperfusion (I/R) injury through targeting hypoxia-inducible factor 1-alpha (HIF-1α). MATERIALS AND METHODS: We constructed rat models with myocardial I/R injury and H9C2 cell models with hypoxia/reoxygenation (H/R) damage. Anti-miR-155 and HIF-1α short hairpin RNA (shRNA) were used to treat rats and H9C2 cells to measure infarct area (IA) by TTC staining, determine creatine kinase (CK) and lactate dehydrogenase (LDH) activities by automatic biochemical analyzer, cardiac troponin T (cTnT) and cardiac troponin I (cTnI) levels by ELISA, and detect apoptosis-related proteins by Western blotting. TUNEL staining and flowcytometry were employed to evaluate the apoptosis, JC-1 staining to detect mitochondrial membrane potential (MMP), and MTT assay to determine H9C2 cell viability. RESULTS: After I/R and H/R, significant elevations were observed in IA, apoptosis, CK, LDH, cTnT, cTnI, and miR-155 levels with reduced HIF-1α. Besides, H/R-induced H9C2 cells presented decreases in MMP and Bcl-2/Bax, but increases in cytosolic/mitochondrial ratio of cytochrome C (Cyt-C) and expressions of cleaved caspase-3 and cleaved caspase-9. However, both rats and H9C2 cells showed an opposite tendency concerning the above after anti-miR-155 treatment. Nevertheless, HIF-1α shRNA effectively reversed protective effects of anti-miR-155 on alleviating I/R- and H/R- induced injury. CONCLUSION: Inhibiting miR-155 could reduce myocardial infarct size, suppress I/R-induced cardiomyocyte apoptosis, and maintain the MMP to alleviate I/R-induced injury via specific regulation of HIF-1α.
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spelling pubmed-68805262019-12-05 Inhibiting miR-155 protects against myocardial ischemia/reperfusion injury via targeted regulation of HIF-1α in rats Chen, Jian-Guo Xu, Xiao-Ming Ji, Hui Sun, Bo Iran J Basic Med Sci Original Article OBJECTIVE(S): The aim of this study was to identify the role of miR-155 in the myocardial ischemia/reperfusion (I/R) injury through targeting hypoxia-inducible factor 1-alpha (HIF-1α). MATERIALS AND METHODS: We constructed rat models with myocardial I/R injury and H9C2 cell models with hypoxia/reoxygenation (H/R) damage. Anti-miR-155 and HIF-1α short hairpin RNA (shRNA) were used to treat rats and H9C2 cells to measure infarct area (IA) by TTC staining, determine creatine kinase (CK) and lactate dehydrogenase (LDH) activities by automatic biochemical analyzer, cardiac troponin T (cTnT) and cardiac troponin I (cTnI) levels by ELISA, and detect apoptosis-related proteins by Western blotting. TUNEL staining and flowcytometry were employed to evaluate the apoptosis, JC-1 staining to detect mitochondrial membrane potential (MMP), and MTT assay to determine H9C2 cell viability. RESULTS: After I/R and H/R, significant elevations were observed in IA, apoptosis, CK, LDH, cTnT, cTnI, and miR-155 levels with reduced HIF-1α. Besides, H/R-induced H9C2 cells presented decreases in MMP and Bcl-2/Bax, but increases in cytosolic/mitochondrial ratio of cytochrome C (Cyt-C) and expressions of cleaved caspase-3 and cleaved caspase-9. However, both rats and H9C2 cells showed an opposite tendency concerning the above after anti-miR-155 treatment. Nevertheless, HIF-1α shRNA effectively reversed protective effects of anti-miR-155 on alleviating I/R- and H/R- induced injury. CONCLUSION: Inhibiting miR-155 could reduce myocardial infarct size, suppress I/R-induced cardiomyocyte apoptosis, and maintain the MMP to alleviate I/R-induced injury via specific regulation of HIF-1α. Mashhad University of Medical Sciences 2019-09 /pmc/articles/PMC6880526/ /pubmed/31807249 http://dx.doi.org/10.22038/ijbms.2019.34853.8270 Text en This is an Open Access article distributed under the terms of the Creative Commons Attribution License, (http://creativecommons.org/licenses/by/3.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Chen, Jian-Guo
Xu, Xiao-Ming
Ji, Hui
Sun, Bo
Inhibiting miR-155 protects against myocardial ischemia/reperfusion injury via targeted regulation of HIF-1α in rats
title Inhibiting miR-155 protects against myocardial ischemia/reperfusion injury via targeted regulation of HIF-1α in rats
title_full Inhibiting miR-155 protects against myocardial ischemia/reperfusion injury via targeted regulation of HIF-1α in rats
title_fullStr Inhibiting miR-155 protects against myocardial ischemia/reperfusion injury via targeted regulation of HIF-1α in rats
title_full_unstemmed Inhibiting miR-155 protects against myocardial ischemia/reperfusion injury via targeted regulation of HIF-1α in rats
title_short Inhibiting miR-155 protects against myocardial ischemia/reperfusion injury via targeted regulation of HIF-1α in rats
title_sort inhibiting mir-155 protects against myocardial ischemia/reperfusion injury via targeted regulation of hif-1α in rats
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6880526/
https://www.ncbi.nlm.nih.gov/pubmed/31807249
http://dx.doi.org/10.22038/ijbms.2019.34853.8270
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