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miR-200a-3p Attenuates Coronary Microembolization-Induced Myocardial Injury in Rats by Inhibiting TXNIP/NLRP3-Mediated Cardiomyocyte Pyroptosis
Coronary microembolization (CME) commonly develops as a complication after percutaneous coronary intervention (PCI), and associated inflammation is a leading driver of myocardial damage. Cardiomyocyte loss in the context of ischemic myocardial disease has been linked to inflammatory pyroptotic cell...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8374895/ https://www.ncbi.nlm.nih.gov/pubmed/34422922 http://dx.doi.org/10.3389/fcvm.2021.693257 |
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author | Chen, Zhi-Qing Zhou, You Chen, Feng Huang, Jun-Wen Li, Hao-Liang Li, Tao Li, Lang |
author_facet | Chen, Zhi-Qing Zhou, You Chen, Feng Huang, Jun-Wen Li, Hao-Liang Li, Tao Li, Lang |
author_sort | Chen, Zhi-Qing |
collection | PubMed |
description | Coronary microembolization (CME) commonly develops as a complication after percutaneous coronary intervention (PCI), and associated inflammation is a leading driver of myocardial damage. Cardiomyocyte loss in the context of ischemic myocardial disease has been linked to inflammatory pyroptotic cell death. Additionally, miR-200a-3p dysregulation has been linked to myocardial ischemia-reperfusion and many other pathological conditions. However, how miR-200a-3p impacts cardiomyocyte pyroptosis in the context of CME remains to be assessed. Herein, a rat model of CME was established via the injection of microembolic spheres into the left ventricle. When myocardial tissue samples from these rats were analyzed, miR-200a-3p levels were markedly decreased, whereas thioredoxin-interacting protein (TXNIP) levels were increased. The ability of miR-200a-3p to directly target TXNIP and to control its expression was confirmed via dual-luciferase reporter assay. Adeno-associated virus serotype 9-pre-miR-200a-3p (AAV-miR-200a-3p) construct transfection was then employed as a means of upregulating this miRNA in CME model rats. Subsequent assays, including echocardiography, enzyme-linked immunosorbent assays (ELISAs), hematoxylin-eosin (H&E) staining, hematoxylin-basic fuchsin-picric acid (HBFP) staining, TdT-mediated dUTP nick-end labeling (TUNEL) staining, immunofluorescence staining, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blotting revealed that miR-200a-3p overexpression inhibited cardiomyocyte pyroptosis and alleviated CME-induced myocardial injury by inhibiting the TXNIP/NOD-like receptor family pyrin domain-containing 3 (NLRP3) pathway. The ability of miR-200a-3p to protect against CME-induced myocardial injury thus highlights a novel approach to preventing or treating such myocardial damage in clinical settings. |
format | Online Article Text |
id | pubmed-8374895 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-83748952021-08-20 miR-200a-3p Attenuates Coronary Microembolization-Induced Myocardial Injury in Rats by Inhibiting TXNIP/NLRP3-Mediated Cardiomyocyte Pyroptosis Chen, Zhi-Qing Zhou, You Chen, Feng Huang, Jun-Wen Li, Hao-Liang Li, Tao Li, Lang Front Cardiovasc Med Cardiovascular Medicine Coronary microembolization (CME) commonly develops as a complication after percutaneous coronary intervention (PCI), and associated inflammation is a leading driver of myocardial damage. Cardiomyocyte loss in the context of ischemic myocardial disease has been linked to inflammatory pyroptotic cell death. Additionally, miR-200a-3p dysregulation has been linked to myocardial ischemia-reperfusion and many other pathological conditions. However, how miR-200a-3p impacts cardiomyocyte pyroptosis in the context of CME remains to be assessed. Herein, a rat model of CME was established via the injection of microembolic spheres into the left ventricle. When myocardial tissue samples from these rats were analyzed, miR-200a-3p levels were markedly decreased, whereas thioredoxin-interacting protein (TXNIP) levels were increased. The ability of miR-200a-3p to directly target TXNIP and to control its expression was confirmed via dual-luciferase reporter assay. Adeno-associated virus serotype 9-pre-miR-200a-3p (AAV-miR-200a-3p) construct transfection was then employed as a means of upregulating this miRNA in CME model rats. Subsequent assays, including echocardiography, enzyme-linked immunosorbent assays (ELISAs), hematoxylin-eosin (H&E) staining, hematoxylin-basic fuchsin-picric acid (HBFP) staining, TdT-mediated dUTP nick-end labeling (TUNEL) staining, immunofluorescence staining, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blotting revealed that miR-200a-3p overexpression inhibited cardiomyocyte pyroptosis and alleviated CME-induced myocardial injury by inhibiting the TXNIP/NOD-like receptor family pyrin domain-containing 3 (NLRP3) pathway. The ability of miR-200a-3p to protect against CME-induced myocardial injury thus highlights a novel approach to preventing or treating such myocardial damage in clinical settings. Frontiers Media S.A. 2021-08-05 /pmc/articles/PMC8374895/ /pubmed/34422922 http://dx.doi.org/10.3389/fcvm.2021.693257 Text en Copyright © 2021 Chen, Zhou, Chen, Huang, Li, Li and Li. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cardiovascular Medicine Chen, Zhi-Qing Zhou, You Chen, Feng Huang, Jun-Wen Li, Hao-Liang Li, Tao Li, Lang miR-200a-3p Attenuates Coronary Microembolization-Induced Myocardial Injury in Rats by Inhibiting TXNIP/NLRP3-Mediated Cardiomyocyte Pyroptosis |
title | miR-200a-3p Attenuates Coronary Microembolization-Induced Myocardial Injury in Rats by Inhibiting TXNIP/NLRP3-Mediated Cardiomyocyte Pyroptosis |
title_full | miR-200a-3p Attenuates Coronary Microembolization-Induced Myocardial Injury in Rats by Inhibiting TXNIP/NLRP3-Mediated Cardiomyocyte Pyroptosis |
title_fullStr | miR-200a-3p Attenuates Coronary Microembolization-Induced Myocardial Injury in Rats by Inhibiting TXNIP/NLRP3-Mediated Cardiomyocyte Pyroptosis |
title_full_unstemmed | miR-200a-3p Attenuates Coronary Microembolization-Induced Myocardial Injury in Rats by Inhibiting TXNIP/NLRP3-Mediated Cardiomyocyte Pyroptosis |
title_short | miR-200a-3p Attenuates Coronary Microembolization-Induced Myocardial Injury in Rats by Inhibiting TXNIP/NLRP3-Mediated Cardiomyocyte Pyroptosis |
title_sort | mir-200a-3p attenuates coronary microembolization-induced myocardial injury in rats by inhibiting txnip/nlrp3-mediated cardiomyocyte pyroptosis |
topic | Cardiovascular Medicine |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8374895/ https://www.ncbi.nlm.nih.gov/pubmed/34422922 http://dx.doi.org/10.3389/fcvm.2021.693257 |
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