Identify Tcea3 as a novel anti-cardiomyocyte hypertrophy gene involved in fatty acid oxidation and oxidative stress
BackgroundChronic pressure overload triggers pathological cardiac hypertrophy that eventually leads to heart failure. Effective biomarkers and therapeutic targets for heart failure remain to be defined. The aim of this study is to identify key genes associated with pathological cardiac hypertrophy b...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-06-01
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| Series: | Frontiers in Cardiovascular Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcvm.2023.1137429/full |
| _version_ | 1797800340636041216 |
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| author | Yingying Guo Yingying Guo Xian-feng Cen Xian-feng Cen Dan Li Dan Li Hong-liang Qiu Hong-liang Qiu Ya-jie Chen Ya-jie Chen Meng Zhang Meng Zhang Si-hui Huang Si-hui Huang Hao Xia Hao Xia Man Xu Man Xu |
| author_facet | Yingying Guo Yingying Guo Xian-feng Cen Xian-feng Cen Dan Li Dan Li Hong-liang Qiu Hong-liang Qiu Ya-jie Chen Ya-jie Chen Meng Zhang Meng Zhang Si-hui Huang Si-hui Huang Hao Xia Hao Xia Man Xu Man Xu |
| author_sort | Yingying Guo |
| collection | DOAJ |
| description | BackgroundChronic pressure overload triggers pathological cardiac hypertrophy that eventually leads to heart failure. Effective biomarkers and therapeutic targets for heart failure remain to be defined. The aim of this study is to identify key genes associated with pathological cardiac hypertrophy by combining bioinformatics analyses with molecular biology experiments.MethodsComprehensive bioinformatics tools were used to screen genes related to pressure overload-induced cardiac hypertrophy. We identified differentially expressed genes (DEGs) by overlapping three Gene Expression Omnibus (GEO) datasets (GSE5500, GSE1621, and GSE36074). Correlation analysis and BioGPS online tool were used to detect the genes of interest. A mouse model of cardiac remodeling induced by transverse aortic constriction (TAC) was established to verify the expression of the interest gene during cardiac remodeling by RT-PCR and western blot. By using RNA interference technology, the effect of transcription elongation factor A3 (Tcea3) silencing on PE-induced hypertrophy of neonatal rat ventricular myocytes (NRVMs) was detected. Next, gene set enrichment analysis (GSEA) and the online tool ARCHS4 were used to predict the possible signaling pathways, and the fatty acid oxidation relevant pathways were enriched and then verified in NRVMs. Furthermore, the changes of long-chain fatty acid respiration in NRVMs were detected using the Seahorse XFe24 Analyzer. Finally, MitoSOX staining was used to detect the effect of Tcea3 on mitochondrial oxidative stress, and the contents of NADP(H) and GSH/GSSG were detected by relevant kits.ResultsA total of 95 DEGs were identified and Tcea3 was negatively correlated with Nppa, Nppb and Myh7. The expression level of Tcea3 was downregulated during cardiac remodeling both in vivo and in vitro. Knockdown of Tcea3 aggravated cardiomyocyte hypertrophy induced by PE in NRVMs. GSEA and online tool ARCHS4 predict Tcea3 involved in fatty acid oxidation (FAO). Subsequently, RT-PCR results showed that knockdown of Tcea3 up-regulated Ces1d and Pla2g5 mRNA expression levels. In PE induced cardiomyocyte hypertrophy, Tcea3 silencing results in decreased fatty acid utilization, decreased ATP synthesis and increased mitochondrial oxidative stress.ConclusionOur study identifies Tcea3 as a novel anti-cardiac remodeling target by regulating FAO and governing mitochondrial oxidative stress. |
| first_indexed | 2024-03-13T04:32:44Z |
| format | Article |
| id | doaj.art-123ec5a0abfd4e519776d7b152ae74e3 |
| institution | Directory Open Access Journal |
| issn | 2297-055X |
| language | English |
| last_indexed | 2024-03-13T04:32:44Z |
| publishDate | 2023-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cardiovascular Medicine |
| spelling | doaj.art-123ec5a0abfd4e519776d7b152ae74e32023-06-19T08:02:59ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2023-06-011010.3389/fcvm.2023.11374291137429Identify Tcea3 as a novel anti-cardiomyocyte hypertrophy gene involved in fatty acid oxidation and oxidative stressYingying Guo0Yingying Guo1Xian-feng Cen2Xian-feng Cen3Dan Li4Dan Li5Hong-liang Qiu6Hong-liang Qiu7Ya-jie Chen8Ya-jie Chen9Meng Zhang10Meng Zhang11Si-hui Huang12Si-hui Huang13Hao Xia14Hao Xia15Man Xu16Man Xu17Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, ChinaHubei Key Laboratory of Metabolic and Chronic Diseases, Renmin Hospital of Wuhan University, Wuhan, ChinaDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan, ChinaHubei Key Laboratory of Metabolic and Chronic Diseases, Renmin Hospital of Wuhan University, Wuhan, ChinaDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan, ChinaHubei Key Laboratory of Metabolic and Chronic Diseases, Renmin Hospital of Wuhan University, Wuhan, ChinaDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan, ChinaHubei Key Laboratory of Metabolic and Chronic Diseases, Renmin Hospital of Wuhan University, Wuhan, ChinaDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan, ChinaHubei Key Laboratory of Metabolic and Chronic Diseases, Renmin Hospital of Wuhan University, Wuhan, ChinaDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan, ChinaHubei Key Laboratory of Metabolic and Chronic Diseases, Renmin Hospital of Wuhan University, Wuhan, ChinaDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan, ChinaHubei Key Laboratory of Metabolic and Chronic Diseases, Renmin Hospital of Wuhan University, Wuhan, ChinaDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan, ChinaCardiovascular Research Institute, Wuhan University, Wuhan, ChinaDepartment of Cardiology, Renmin Hospital of Wuhan University, Wuhan, ChinaHubei Key Laboratory of Metabolic and Chronic Diseases, Renmin Hospital of Wuhan University, Wuhan, ChinaBackgroundChronic pressure overload triggers pathological cardiac hypertrophy that eventually leads to heart failure. Effective biomarkers and therapeutic targets for heart failure remain to be defined. The aim of this study is to identify key genes associated with pathological cardiac hypertrophy by combining bioinformatics analyses with molecular biology experiments.MethodsComprehensive bioinformatics tools were used to screen genes related to pressure overload-induced cardiac hypertrophy. We identified differentially expressed genes (DEGs) by overlapping three Gene Expression Omnibus (GEO) datasets (GSE5500, GSE1621, and GSE36074). Correlation analysis and BioGPS online tool were used to detect the genes of interest. A mouse model of cardiac remodeling induced by transverse aortic constriction (TAC) was established to verify the expression of the interest gene during cardiac remodeling by RT-PCR and western blot. By using RNA interference technology, the effect of transcription elongation factor A3 (Tcea3) silencing on PE-induced hypertrophy of neonatal rat ventricular myocytes (NRVMs) was detected. Next, gene set enrichment analysis (GSEA) and the online tool ARCHS4 were used to predict the possible signaling pathways, and the fatty acid oxidation relevant pathways were enriched and then verified in NRVMs. Furthermore, the changes of long-chain fatty acid respiration in NRVMs were detected using the Seahorse XFe24 Analyzer. Finally, MitoSOX staining was used to detect the effect of Tcea3 on mitochondrial oxidative stress, and the contents of NADP(H) and GSH/GSSG were detected by relevant kits.ResultsA total of 95 DEGs were identified and Tcea3 was negatively correlated with Nppa, Nppb and Myh7. The expression level of Tcea3 was downregulated during cardiac remodeling both in vivo and in vitro. Knockdown of Tcea3 aggravated cardiomyocyte hypertrophy induced by PE in NRVMs. GSEA and online tool ARCHS4 predict Tcea3 involved in fatty acid oxidation (FAO). Subsequently, RT-PCR results showed that knockdown of Tcea3 up-regulated Ces1d and Pla2g5 mRNA expression levels. In PE induced cardiomyocyte hypertrophy, Tcea3 silencing results in decreased fatty acid utilization, decreased ATP synthesis and increased mitochondrial oxidative stress.ConclusionOur study identifies Tcea3 as a novel anti-cardiac remodeling target by regulating FAO and governing mitochondrial oxidative stress.https://www.frontiersin.org/articles/10.3389/fcvm.2023.1137429/fullheart failurebioinformaticsTcea3transcriptional regulatorfatty acid oxidation |
| spellingShingle | Yingying Guo Yingying Guo Xian-feng Cen Xian-feng Cen Dan Li Dan Li Hong-liang Qiu Hong-liang Qiu Ya-jie Chen Ya-jie Chen Meng Zhang Meng Zhang Si-hui Huang Si-hui Huang Hao Xia Hao Xia Man Xu Man Xu Identify Tcea3 as a novel anti-cardiomyocyte hypertrophy gene involved in fatty acid oxidation and oxidative stress Frontiers in Cardiovascular Medicine heart failure bioinformatics Tcea3 transcriptional regulator fatty acid oxidation |
| title | Identify Tcea3 as a novel anti-cardiomyocyte hypertrophy gene involved in fatty acid oxidation and oxidative stress |
| title_full | Identify Tcea3 as a novel anti-cardiomyocyte hypertrophy gene involved in fatty acid oxidation and oxidative stress |
| title_fullStr | Identify Tcea3 as a novel anti-cardiomyocyte hypertrophy gene involved in fatty acid oxidation and oxidative stress |
| title_full_unstemmed | Identify Tcea3 as a novel anti-cardiomyocyte hypertrophy gene involved in fatty acid oxidation and oxidative stress |
| title_short | Identify Tcea3 as a novel anti-cardiomyocyte hypertrophy gene involved in fatty acid oxidation and oxidative stress |
| title_sort | identify tcea3 as a novel anti cardiomyocyte hypertrophy gene involved in fatty acid oxidation and oxidative stress |
| topic | heart failure bioinformatics Tcea3 transcriptional regulator fatty acid oxidation |
| url | https://www.frontiersin.org/articles/10.3389/fcvm.2023.1137429/full |
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