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bioRxiv · 10.1101/2020.07.27.220954

Molecular mechanisms of Cardiac Injury associated with myocardial SARS-CoV-2 infection

Liu, X.·Lou, L.·Zhou, L.
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Abstract

BackgroundCoronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread around the world. Developing cardiac injury is a common condition in COVID-19 patients, but the pathogenesis remains unclear. MethodsThe RNA-Seq dataset (GES150392) compared expression profiling of mock human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and SARS-cov-2-infected hiPSC-CMs were obtained from Gene Expression Omnibus (GEO). We identified the differentially expressed genes (DEGs) between those two groups. Through gene set enrichment analysis (GSEA), Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and CLINVAR human diseases analysis to identify the main effect of SARS-CoV-2 on cardiomyocytes. A protein-protein interaction (PPI) network was constructed to visualize interactions and functions of the hub genes. ResultsA total of 1554 DEGs were identified (726 upregulated genes and 828 downregulated genes). Gene enrichment analysis shown that SARS-CoV-2 activate immuno-inflammatory responses via multiple signal pathways, including TNF, IL6-JAK-STAT3, IL2-STAT5, NF-{kappa}B, IL17, and Toll-like receptor signaling pathway in hiPSC-CMs. Whereas, the muscle contraction, cellular respiration and cell cycle of hiPSC-CMs were inhibited by SARS-CoV-2. CLINVAR human diseases analysis shown SRAS-Cov-2 infection was associated with myocardial infarction, cardiomyopathy and Limb-girdle muscular dystrophy. 15 hub genes were identified based on PPI network. Function analysis revealed that 11 upregulated hub genes were mainly enriched in cytokine activity, chemokine activity, Inflammatory response, leukocyte chemotaxis, and lipopolysaccharide-mediated signaling pathway. Furthermore, 4 downregulated hub genes were related to cell cycle regulation. ConclusionThe present study elucidates that the SARS-CoV-2 infection induced a strong defensive response in cardiomyocyte, leading to excessive immune inflammation, cell hypoxia, functional contractility reduction and apoptosis, ultimately result in myocardial injury.

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Liu, X., Lou, L., Zhou, L.. 2020-07-27. Molecular mechanisms of Cardiac Injury associated with myocardial SARS-CoV-2 infection. https://doi.org/10.1101/2020.07.27.220954

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