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pmid:36958170

The molecular mechanism of cardiac injury in SARS-CoV-2 infection: Focus on mitochondrial dysfunction.

Yang Shen · Min Chen · Wei Gu · Jianwei Wan · Zhihui Cheng · Kan Shen · Wen Zhang · Jinming He · Yunfeng Wang · Xingqi Deng

Journal of infection and public health · 2023 doi:10.1016/j.jiph.2023.03.015

Paper

complete

Experiment

complete

Data

partial

Analysis

complete

Execution

absent

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Record details sci_version · id · kind · revision · content_hash · schema · created_at · updated_at · generator
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title
The molecular mechanism of cardiac injury in SARS-CoV-2 infection: Focus on mitochondrial dysfunction.
doi
10.1016/j.jiph.2023.03.015
pmid
36958170
authors array · 10 items
[0]
Yang Shen
[1]
Min Chen
[2]
Wei Gu
[3]
Jianwei Wan
[4]
Zhihui Cheng
[5]
Kan Shen
[6]
Wen Zhang
[7]
Jinming He
[8]
Yunfeng Wang
[9]
Xingqi Deng
journal
Journal of infection and public health
year
2023
abstract
BACKGROUND: Coronavirus disease 2019(COVID-19) caused a large number of infections worldwide. Although some patients recovered from the disease, some of the other problems that accompanied it, such as cardiac injury, could affect the patient's subsequent quality of life and prognosis. OBJECTIVES: To clarify the molecular mechanism of cardiac injury in SARS-CoV-2 Infection. METHODS: The RNA-Seq dataset (GSE184715) comparing expression profiling of Mock human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and SARS-CoV-2-infected hiPSC-CMs was downloaded from Gene Expression Omnibus (GEO). Differentially expressed genes(DEGs) were performed by the R software. Degs were analyzed by enrichment analysis to clarify the affected pathways. Hub genes were screened out by a PPI network constructed from Degs. Finally, Connectivity Map was used to screen for the treatment of COVID-19 induced cardiac injury. RESULTS: 2705 differentially expressed genes were identified. Enrichment analysis confirmed that mitochondrial dysfunction was caused by SARS-CoV-2, meanwhile, cardiac muscle contraction was suppressed and NF-κB was activated. Based on the PPI network, 15 hub genes were identified. These 15 down-regulated hub genes were mainly involved in the reduced activity of complexes in the mitochondrial respiratory chain associated with mitochondrial dysfunction. Moreover, 5 candidate drugs were identified to treat cardiac injury. CONCLUSION: In conclusion, SARS-CoV-2 infection of cardiomyocytes causes mitochondrial dysfunction, including reduced mitochondrial respiratory chain complex activity and decreased ATP synthesis, leading to cardiomyocyte apoptosis, while the activated NF-κB also induced cytokine storms, ultimately resulting in cardiac injury.
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The R(version 4.2.1, https://www.R-project.org/) package “DESeq2″ (version 1.36.0) [9] was used to identify the differential gene expression(DEGs) and the threshold was set as Padj< 0.001 and |log2FoldChange |> 2.
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The R(version 4.2.1, https://www.R-project.org/) package “DESeq2″ (version 1.36.0) [9] was used to identify the differential gene expression(DEGs) and the threshold was set as Padj< 0.001 and |log2FoldChange |> 2.
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The RNA-seq data(GSE184715) was obtained from the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO Datasets). The GSE184715 dataset contained the Mock group and the Infection group, each with 3 samples, for a total of 6 samples. Samples in the infection group(Infection1–3, GSM5596065–7) were obtained from the infection of human-induced pluripotent stem cell-derived cardiomyocytes(hiPSC-CMs) with SARS-COV-2 for 48 h. The Mock group(Mock1–3, GSM5596062–4) was treated with mock.
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The RNA-seq data(GSE184715) was obtained from the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO Datasets). The GSE184715 dataset contained the Mock group and the Infection group, each with 3 samples, for a total of 6 samples. Samples in the infection group(Infection1–3, GSM5596065–7) were obtained from the infection of human-induced pluripotent stem cell-derived cardiomyocytes(hiPSC-CMs) with SARS-COV-2 for 48 h. The Mock group(Mock1–3, GSM5596062–4) was treated with mock.
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SARS-CoV-2 infection of cardiomyocytes causes mitochondrial dysfunction, including reduced mitochondrial respiratory chain complex activity and decreased ATP synthesis, leading to cardiomyocyte apoptosis, while the activated NF-κB also induced cytokine storms, ultimately resulting in cardiac injury.
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In conclusion, SARS-CoV-2 infection of cardiomyocytes causes mitochondrial dysfunction, including reduced mitochondrial respiratory chain complex activity and decreased ATP synthesis, leading to cardiomyocyte apoptosis, while the activated NF-κB also induced cytokine storms, ultimately resulting in cardiac injury.
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SARS-CoV-2 infection of cardiomyocytes causes mitochondrial dysfunction, including reduced mitochondrial respiratory chain complex activity and decreased ATP synthesis, leading to cardiomyocyte apoptosis, while the activated NF-κB also induced cytokine storms, ultimately resulting in cardiac injury.
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The RNA-seq data(GSE184715) was obtained from the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO Datasets). The GSE184715 dataset contained the Mock group and the Infection group, each with 3 samples, for a total of 6 samples. Samples in the infection group(Infection1–3, GSM5596065–7) were obtained from the infection of human-induced pluripotent stem cell-derived cardiomyocytes(hiPSC-CMs) with SARS-COV-2 for 48 h. The Mock group(Mock1–3, GSM5596062–4) was treated with mock.
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Highly efficient SARS-CoV-2 infection of human cardiomyocytes: spike protein-mediated cell fusion and its inhibition
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The R(version 4.2.1, https://www.R-project.org/) package “DESeq2″ (version 1.36.0) [9] was used to identify the differential gene expression(DEGs) and the threshold was set as Padj< 0.001 and |log2FoldChange |> 2.
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The RNA-seq data(GSE184715) was obtained from the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO Datasets). The GSE184715 dataset contained the Mock group and the Infection group, each with 3 samples, for a total of 6 samples. Samples in the infection group(Infection1–3, GSM5596065–7) were obtained from the infection of human-induced pluripotent stem cell-derived cardiomyocytes(hiPSC-CMs) with SARS-COV-2 for 48 h. The Mock group(Mock1–3, GSM5596062–4) was treated with mock.
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injury in SARS-CoV-2 Infection. METHODS: The RNA-Seq dataset (GSE184715) comparing expression pro
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Complete file
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Although some patients recovered from the disease, some of the other problems that accompanied it, such as cardiac injury, could affect the patient's subsequent quality of life and prognosis.\nOBJECTIVES: To clarify the molecular mechanism of cardiac injury in SARS-CoV-2 Infection.\nMETHODS: The RNA-Seq dataset (GSE184715) comparing expression profiling of Mock human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and SARS-CoV-2-infected hiPSC-CMs was downloaded from Gene Expression Omnibus (GEO). Differentially expressed genes(DEGs) were performed by the R software. Degs were analyzed by enrichment analysis to clarify the affected pathways. Hub genes were screened out by a PPI network constructed from Degs. Finally, Connectivity Map was used to screen for the treatment of COVID-19 induced cardiac injury.\nRESULTS: 2705 differentially expressed genes were identified. Enrichment analysis confirmed that mitochondrial dysfunction was caused by SARS-CoV-2, meanwhile, cardiac muscle contraction was suppressed and NF-κB was activated. Based on the PPI network, 15 hub genes were identified. These 15 down-regulated hub genes were mainly involved in the reduced activity of complexes in the mitochondrial respiratory chain associated with mitochondrial dysfunction. Moreover, 5 candidate drugs were identified to treat cardiac injury.\nCONCLUSION: In conclusion, SARS-CoV-2 infection of cardiomyocytes causes mitochondrial dysfunction, including reduced mitochondrial respiratory chain complex activity and decreased ATP synthesis, leading to cardiomyocyte apoptosis, while the activated NF-κB also induced cytokine storms, ultimately resulting in cardiac injury.", "claims": [{"id": "claim-method", "statement": "The R(version 4.2.1, https://www.R-project.org/) package “DESeq2″ (version 1.36.0) [9] was used to identify the differential gene expression(DEGs) and the threshold was set as Padj< 0.001 and |log2FoldChange |> 2.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36958170", "locator": "sections[4] \"Differential gene expression analysis\" paragraph 2", "quote": "The R(version 4.2.1, https://www.R-project.org/) package “DESeq2″ (version 1.36.0) [9] was used to identify the differential gene expression(DEGs) and the threshold was set as Padj< 0.001 and |log2FoldChange |> 2."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The RNA-seq data(GSE184715) was obtained from the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO Datasets). 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The GSE184715 dataset contained the Mock group and the Infection group, each with 3 samples, for a total of 6 samples. Samples in the infection group(Infection1–3, GSM5596065–7) were obtained from the infection of human-induced pluripotent stem cell-derived cardiomyocytes(hiPSC-CMs) with SARS-COV-2 for 48 h. The Mock group(Mock1–3, GSM5596062–4) was treated with mock.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The RNA-seq data(GSE184715) was obtained from the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO Datasets). The GSE184715 dataset contained the Mock group and the Infection group, each with 3 samples, for a total of 6 samples. Samples in the infection group(Infection1–3, GSM5596065–7) were obtained from the infection of human-induced pluripotent stem cell-derived cardiomyocytes(hiPSC-CMs) with SARS-COV-2 for 48 h. 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