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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
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Experiment
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Data
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Analysis
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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 Mock group(Mock1–3, GSM5596062–4) was treated with mock."}], "state": "complete"}, {"id": "claim-target-result", "statement": "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.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36958170", "locator": "sections[0] \"Abstract\" paragraph 5", "quote": "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."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "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.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:36958170"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE184715"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE184715"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:36958170", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1016/j.jiph.2023.03.015", "sha256": "sha256:0dd116e4ccbb7d8b672e8ee12b5a167d7da0035e6784f7fdf8d124ba70b05b72", "bytes": 27890, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1016/j.jiph.2023.03.015", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10019919", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE184715", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE184715", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE184715", "version": null, "note": "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.", "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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