Dysregulated autophagy-related genes in septic cardiomyopathy: Comprehensive bioinformatics analysis based on the human transcriptomes and experimental validation
Septic cardiomyopathy (SCM) is severe organ dysfunction caused by sepsis that is associated with poor prognosis, and its pathobiological mechanisms remain unclear. Autophagy is a biological process that has recently been focused on SCM, yet the current understanding of the role of dysregulated autop...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Cardiovascular Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcvm.2022.923066/full |
| _version_ | 1828519181178372096 |
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| author | Hua-Xi Zou Hua-Xi Zou Hua-Xi Zou Bai-Quan Qiu Bai-Quan Qiu Ze-Yu Zhang Tie Hu Tie Hu Li Wan Li Wan Ji-Chun Liu Ji-Chun Liu Ji-Chun Liu Huang Huang Huang Huang Song-Qing Lai Song-Qing Lai |
| author_facet | Hua-Xi Zou Hua-Xi Zou Hua-Xi Zou Bai-Quan Qiu Bai-Quan Qiu Ze-Yu Zhang Tie Hu Tie Hu Li Wan Li Wan Ji-Chun Liu Ji-Chun Liu Ji-Chun Liu Huang Huang Huang Huang Song-Qing Lai Song-Qing Lai |
| author_sort | Hua-Xi Zou |
| collection | DOAJ |
| description | Septic cardiomyopathy (SCM) is severe organ dysfunction caused by sepsis that is associated with poor prognosis, and its pathobiological mechanisms remain unclear. Autophagy is a biological process that has recently been focused on SCM, yet the current understanding of the role of dysregulated autophagy in the pathogenesis of SCM remains limited and uncertain. Exploring the molecular mechanisms of disease based on the transcriptomes of human pathological samples may bring the closest insights. In this study, we analyzed the differential expression of autophagy-related genes in SCM based on the transcriptomes of human septic hearts, and further explored their potential crosstalk and functional pathways. Key functional module and hub genes were identified by constructing a protein–protein interaction network. Eight key genes (CCL2, MYC, TP53, SOD2, HIF1A, CTNNB1, CAT, and ADIPOQ) that regulate autophagy in SCM were identified after validation in a lipopolysaccharide (LPS)-induced H9c2 cardiomyoblast injury model, as well as the autophagic characteristic features. Furthermore, we found that key genes were associated with abnormal immune infiltration in septic hearts and have the potential to serve as biomarkers. Finally, we predicted drugs that may play a protective role in SCM by regulating autophagy based on our results. Our study provides evidence and new insights into the role of autophagy in SCM based on human septic heart transcriptomes, which would be of great benefit to reveal the molecular pathological mechanisms and explore the diagnostic and therapeutic targets for SCM. |
| first_indexed | 2024-12-11T19:07:28Z |
| format | Article |
| id | doaj.art-25d7acc67de14f0882a88a8b873f9722 |
| institution | Directory Open Access Journal |
| issn | 2297-055X |
| language | English |
| last_indexed | 2024-12-11T19:07:28Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cardiovascular Medicine |
| spelling | doaj.art-25d7acc67de14f0882a88a8b873f97222022-12-22T00:53:51ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2022-08-01910.3389/fcvm.2022.923066923066Dysregulated autophagy-related genes in septic cardiomyopathy: Comprehensive bioinformatics analysis based on the human transcriptomes and experimental validationHua-Xi Zou0Hua-Xi Zou1Hua-Xi Zou2Bai-Quan Qiu3Bai-Quan Qiu4Ze-Yu Zhang5Tie Hu6Tie Hu7Li Wan8Li Wan9Ji-Chun Liu10Ji-Chun Liu11Ji-Chun Liu12Huang Huang13Huang Huang14Song-Qing Lai15Song-Qing Lai16Department of Cardiovascular Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, ChinaInstitute of Cardiovascular Diseases, Jiangxi Academy of Clinical Medical Sciences, The First Affiliated Hospital of Nanchang University, Nanchang, ChinaDepartment of Cardiovascular Surgery, Second Affiliated Hospital of Nanchang University, Nanchang, ChinaInstitute of Cardiovascular Diseases, Jiangxi Academy of Clinical Medical Sciences, The First Affiliated Hospital of Nanchang University, Nanchang, ChinaDepartment of Cardiovascular Surgery, Second Affiliated Hospital of Nanchang University, Nanchang, ChinaInstitute of Nanchang University Trauma Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, ChinaInstitute of Cardiovascular Diseases, Jiangxi Academy of Clinical Medical Sciences, The First Affiliated Hospital of Nanchang University, Nanchang, ChinaDepartment of Cardiovascular Surgery, Second Affiliated Hospital of Nanchang University, Nanchang, ChinaDepartment of Cardiovascular Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, ChinaInstitute of Cardiovascular Diseases, Jiangxi Academy of Clinical Medical Sciences, The First Affiliated Hospital of Nanchang University, Nanchang, ChinaDepartment of Cardiovascular Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, ChinaInstitute of Cardiovascular Diseases, Jiangxi Academy of Clinical Medical Sciences, The First Affiliated Hospital of Nanchang University, Nanchang, ChinaDepartment of Cardiovascular Surgery, Second Affiliated Hospital of Nanchang University, Nanchang, ChinaDepartment of Cardiovascular Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, ChinaInstitute of Cardiovascular Diseases, Jiangxi Academy of Clinical Medical Sciences, The First Affiliated Hospital of Nanchang University, Nanchang, ChinaDepartment of Cardiovascular Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, ChinaInstitute of Cardiovascular Diseases, Jiangxi Academy of Clinical Medical Sciences, The First Affiliated Hospital of Nanchang University, Nanchang, ChinaSeptic cardiomyopathy (SCM) is severe organ dysfunction caused by sepsis that is associated with poor prognosis, and its pathobiological mechanisms remain unclear. Autophagy is a biological process that has recently been focused on SCM, yet the current understanding of the role of dysregulated autophagy in the pathogenesis of SCM remains limited and uncertain. Exploring the molecular mechanisms of disease based on the transcriptomes of human pathological samples may bring the closest insights. In this study, we analyzed the differential expression of autophagy-related genes in SCM based on the transcriptomes of human septic hearts, and further explored their potential crosstalk and functional pathways. Key functional module and hub genes were identified by constructing a protein–protein interaction network. Eight key genes (CCL2, MYC, TP53, SOD2, HIF1A, CTNNB1, CAT, and ADIPOQ) that regulate autophagy in SCM were identified after validation in a lipopolysaccharide (LPS)-induced H9c2 cardiomyoblast injury model, as well as the autophagic characteristic features. Furthermore, we found that key genes were associated with abnormal immune infiltration in septic hearts and have the potential to serve as biomarkers. Finally, we predicted drugs that may play a protective role in SCM by regulating autophagy based on our results. Our study provides evidence and new insights into the role of autophagy in SCM based on human septic heart transcriptomes, which would be of great benefit to reveal the molecular pathological mechanisms and explore the diagnostic and therapeutic targets for SCM.https://www.frontiersin.org/articles/10.3389/fcvm.2022.923066/fullsepsis cardiomyopathyautophagytranscriptomekey genesdatabase |
| spellingShingle | Hua-Xi Zou Hua-Xi Zou Hua-Xi Zou Bai-Quan Qiu Bai-Quan Qiu Ze-Yu Zhang Tie Hu Tie Hu Li Wan Li Wan Ji-Chun Liu Ji-Chun Liu Ji-Chun Liu Huang Huang Huang Huang Song-Qing Lai Song-Qing Lai Dysregulated autophagy-related genes in septic cardiomyopathy: Comprehensive bioinformatics analysis based on the human transcriptomes and experimental validation Frontiers in Cardiovascular Medicine sepsis cardiomyopathy autophagy transcriptome key genes database |
| title | Dysregulated autophagy-related genes in septic cardiomyopathy: Comprehensive bioinformatics analysis based on the human transcriptomes and experimental validation |
| title_full | Dysregulated autophagy-related genes in septic cardiomyopathy: Comprehensive bioinformatics analysis based on the human transcriptomes and experimental validation |
| title_fullStr | Dysregulated autophagy-related genes in septic cardiomyopathy: Comprehensive bioinformatics analysis based on the human transcriptomes and experimental validation |
| title_full_unstemmed | Dysregulated autophagy-related genes in septic cardiomyopathy: Comprehensive bioinformatics analysis based on the human transcriptomes and experimental validation |
| title_short | Dysregulated autophagy-related genes in septic cardiomyopathy: Comprehensive bioinformatics analysis based on the human transcriptomes and experimental validation |
| title_sort | dysregulated autophagy related genes in septic cardiomyopathy comprehensive bioinformatics analysis based on the human transcriptomes and experimental validation |
| topic | sepsis cardiomyopathy autophagy transcriptome key genes database |
| url | https://www.frontiersin.org/articles/10.3389/fcvm.2022.923066/full |
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