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HMGCS2 silencing attenuates high glucose-induced in vitro diabetic cardiomyopathy by increasing cell viability, and inhibiting apoptosis, inflammation, and oxidative stress
Diabetic cardiomyopathy (DCM) is a diabetic mellitus-related complications and progression of DCM may eventually lead to heart failure, while mechanisms related to DCM pathophysiology remain unclear. The study was undertaken to identify possible hub genes associated with DCM progression through bioi...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Taylor & Francis
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9275940/ https://www.ncbi.nlm.nih.gov/pubmed/35506308 http://dx.doi.org/10.1080/21655979.2022.2063222 |
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author | Chen, Donglin Ruan, Xiang Liu, Yu He, Yan |
author_facet | Chen, Donglin Ruan, Xiang Liu, Yu He, Yan |
author_sort | Chen, Donglin |
collection | PubMed |
description | Diabetic cardiomyopathy (DCM) is a diabetic mellitus-related complications and progression of DCM may eventually lead to heart failure, while mechanisms related to DCM pathophysiology remain unclear. The study was undertaken to identify possible hub genes associated with DCM progression through bioinformatics analysis and to validate the role of 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2) in DCM progression using a cellular model of high glucose (HG)-induced DCM. The common differentially expressed genes (DEGs) between GSE173884 and GSE161827 were used for PPI network analysis. Our results identified 17 common DEGs between GSE173384 and GSE161827. Further analysis of the protein–protein interaction network identified nine hub genes and HMGCS2. The in vitro functional assays showed that HG induced up-regulation of HMGCS2, suppressed cardiomyocyte viability, enhanced apoptosis, inflammation, and oxidative stress of cardiomyocytes. Gain-of-function assays showed that HMGCS2 overexpression reduced cell viability, increased apoptosis, caspase-3/-9 activity, up-regulated interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α) expression, decreased superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase expression, increased malondialdehyde (MDA) content, and reactive oxygen species (ROS) level but inhibited total antioxidant activity, SOD activity, CAT activity, and glutathione content in cardiomyocytes. Rescue experiments demonstrated HMGCS2 silence attenuated HG-induced decrease in cardiomyocyte viability and increase in cardiomyocyte apoptosis, inflammation, and oxidative stress. All in all, our study identified HMGCS2 as a hub gene in DCM pathophysiology and further functional studies indicated that HMGCS2 may aggravate DCM progression by reducing cardiomyocyte viability, increasing cardiomyocyte apoptosis, and promoting inflammation and oxidative stress in cardiomyocytes. |
format | Online Article Text |
id | pubmed-9275940 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-92759402022-07-13 HMGCS2 silencing attenuates high glucose-induced in vitro diabetic cardiomyopathy by increasing cell viability, and inhibiting apoptosis, inflammation, and oxidative stress Chen, Donglin Ruan, Xiang Liu, Yu He, Yan Bioengineered Research Paper Diabetic cardiomyopathy (DCM) is a diabetic mellitus-related complications and progression of DCM may eventually lead to heart failure, while mechanisms related to DCM pathophysiology remain unclear. The study was undertaken to identify possible hub genes associated with DCM progression through bioinformatics analysis and to validate the role of 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2) in DCM progression using a cellular model of high glucose (HG)-induced DCM. The common differentially expressed genes (DEGs) between GSE173884 and GSE161827 were used for PPI network analysis. Our results identified 17 common DEGs between GSE173384 and GSE161827. Further analysis of the protein–protein interaction network identified nine hub genes and HMGCS2. The in vitro functional assays showed that HG induced up-regulation of HMGCS2, suppressed cardiomyocyte viability, enhanced apoptosis, inflammation, and oxidative stress of cardiomyocytes. Gain-of-function assays showed that HMGCS2 overexpression reduced cell viability, increased apoptosis, caspase-3/-9 activity, up-regulated interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α) expression, decreased superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase expression, increased malondialdehyde (MDA) content, and reactive oxygen species (ROS) level but inhibited total antioxidant activity, SOD activity, CAT activity, and glutathione content in cardiomyocytes. Rescue experiments demonstrated HMGCS2 silence attenuated HG-induced decrease in cardiomyocyte viability and increase in cardiomyocyte apoptosis, inflammation, and oxidative stress. All in all, our study identified HMGCS2 as a hub gene in DCM pathophysiology and further functional studies indicated that HMGCS2 may aggravate DCM progression by reducing cardiomyocyte viability, increasing cardiomyocyte apoptosis, and promoting inflammation and oxidative stress in cardiomyocytes. Taylor & Francis 2022-05-04 /pmc/articles/PMC9275940/ /pubmed/35506308 http://dx.doi.org/10.1080/21655979.2022.2063222 Text en © 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Paper Chen, Donglin Ruan, Xiang Liu, Yu He, Yan HMGCS2 silencing attenuates high glucose-induced in vitro diabetic cardiomyopathy by increasing cell viability, and inhibiting apoptosis, inflammation, and oxidative stress |
title | HMGCS2 silencing attenuates high glucose-induced in vitro diabetic cardiomyopathy by increasing cell viability, and inhibiting apoptosis, inflammation, and oxidative stress |
title_full | HMGCS2 silencing attenuates high glucose-induced in vitro diabetic cardiomyopathy by increasing cell viability, and inhibiting apoptosis, inflammation, and oxidative stress |
title_fullStr | HMGCS2 silencing attenuates high glucose-induced in vitro diabetic cardiomyopathy by increasing cell viability, and inhibiting apoptosis, inflammation, and oxidative stress |
title_full_unstemmed | HMGCS2 silencing attenuates high glucose-induced in vitro diabetic cardiomyopathy by increasing cell viability, and inhibiting apoptosis, inflammation, and oxidative stress |
title_short | HMGCS2 silencing attenuates high glucose-induced in vitro diabetic cardiomyopathy by increasing cell viability, and inhibiting apoptosis, inflammation, and oxidative stress |
title_sort | hmgcs2 silencing attenuates high glucose-induced in vitro diabetic cardiomyopathy by increasing cell viability, and inhibiting apoptosis, inflammation, and oxidative stress |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9275940/ https://www.ncbi.nlm.nih.gov/pubmed/35506308 http://dx.doi.org/10.1080/21655979.2022.2063222 |
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