Exploring the underlying molecular mechanisms of acute myocardial infarction after SARS-CoV-2 infection

An increase in acute myocardial infarction (AMI)-related deaths has been reported during the COVID-19 pandemic. Despite evidence suggesting the association between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and AMI, the underlying mechanisms remain unclear. Here, we integ...

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Main Authors: Xie, Enrui, Shen, Xiaotao, Yeo, Yee Hui, Xing, Zixuan, Ebinger, Joseph E., Duan, Yixuan, Zhang, Yue, Cheng, Susan, Ji, Fanpu, Deng, Jie
Other Authors: Lee Kong Chian School of Medicine (LKCMedicine)
Format: Article
Language:English
Published: 2024
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Online Access:https://hdl.handle.net/10356/181577
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Institution: Nanyang Technological University
Language: English
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spelling sg-ntu-dr.10356-1815772024-12-15T15:38:51Z Exploring the underlying molecular mechanisms of acute myocardial infarction after SARS-CoV-2 infection Xie, Enrui Shen, Xiaotao Yeo, Yee Hui Xing, Zixuan Ebinger, Joseph E. Duan, Yixuan Zhang, Yue Cheng, Susan Ji, Fanpu Deng, Jie Lee Kong Chian School of Medicine (LKCMedicine) Medicine, Health and Life Sciences SARS-CoV-2 Acute myocardial infarction An increase in acute myocardial infarction (AMI)-related deaths has been reported during the COVID-19 pandemic. Despite evidence suggesting the association between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and AMI, the underlying mechanisms remain unclear. Here, we integrated mRNA and microRNA expression profiles related to SARS-CoV-2 infection and AMI from public databases. We then performed transcriptomic analysis using bioinformatics and systems biology approaches to explore the potential molecular mechanisms of SARS-CoV-2 infection affects AMI. First, twenty-one common differentially expressed genes (DEGs) were identified from SARS-CoV-2 infection and AMI patients in endothelial cells datasets and then we performed functional analysis to predict the roles of these DEGs. The functional analysis emphasized that the endothelial cell response to cytokine stimulus due to excessive inflammation was essential in these two diseases. Importantly, the tumor necrosis factor and interleukin-17 signaling pathways appeared to be integral factors in this mechanism. Interestingly, most of these common genes were also upregulated in transcriptomic datasets of SARS-CoV-2-infected cardiomyocytes, suggesting that these genes may be shared in cardiac- and vascular-related injuries. We subsequently built a protein-protein interaction network and extracted hub genes and essential modules from this network. At the transcriptional and post-transcriptional levels, regulatory networks with common DEGs were also constructed, and some key regulator signatures were further identified and validated. In summary, our research revealed that a highly activated inflammatory response in patients with COVID-19 might be a crucial factor for susceptibility to AMI and we identified some candidate genes and regulators that could be used as biomarkers or potential therapeutic targets. Published version 2024-12-10T00:50:30Z 2024-12-10T00:50:30Z 2024 Journal Article Xie, E., Shen, X., Yeo, Y. H., Xing, Z., Ebinger, J. E., Duan, Y., Zhang, Y., Cheng, S., Ji, F. & Deng, J. (2024). Exploring the underlying molecular mechanisms of acute myocardial infarction after SARS-CoV-2 infection. American Heart Journal Plus : Cardiology Research and Practice, 44, 100417-. https://dx.doi.org/10.1016/j.ahjo.2024.100417 2666-6022 https://hdl.handle.net/10356/181577 10.1016/j.ahjo.2024.100417 39045234 2-s2.0-85197084427 44 100417 en American Heart Journal Plus : Cardiology Research and Practice © 2024 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC license (http://creativecommons.org/licenses/bync/4.0/). application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Medicine, Health and Life Sciences
SARS-CoV-2
Acute myocardial infarction
spellingShingle Medicine, Health and Life Sciences
SARS-CoV-2
Acute myocardial infarction
Xie, Enrui
Shen, Xiaotao
Yeo, Yee Hui
Xing, Zixuan
Ebinger, Joseph E.
Duan, Yixuan
Zhang, Yue
Cheng, Susan
Ji, Fanpu
Deng, Jie
Exploring the underlying molecular mechanisms of acute myocardial infarction after SARS-CoV-2 infection
description An increase in acute myocardial infarction (AMI)-related deaths has been reported during the COVID-19 pandemic. Despite evidence suggesting the association between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and AMI, the underlying mechanisms remain unclear. Here, we integrated mRNA and microRNA expression profiles related to SARS-CoV-2 infection and AMI from public databases. We then performed transcriptomic analysis using bioinformatics and systems biology approaches to explore the potential molecular mechanisms of SARS-CoV-2 infection affects AMI. First, twenty-one common differentially expressed genes (DEGs) were identified from SARS-CoV-2 infection and AMI patients in endothelial cells datasets and then we performed functional analysis to predict the roles of these DEGs. The functional analysis emphasized that the endothelial cell response to cytokine stimulus due to excessive inflammation was essential in these two diseases. Importantly, the tumor necrosis factor and interleukin-17 signaling pathways appeared to be integral factors in this mechanism. Interestingly, most of these common genes were also upregulated in transcriptomic datasets of SARS-CoV-2-infected cardiomyocytes, suggesting that these genes may be shared in cardiac- and vascular-related injuries. We subsequently built a protein-protein interaction network and extracted hub genes and essential modules from this network. At the transcriptional and post-transcriptional levels, regulatory networks with common DEGs were also constructed, and some key regulator signatures were further identified and validated. In summary, our research revealed that a highly activated inflammatory response in patients with COVID-19 might be a crucial factor for susceptibility to AMI and we identified some candidate genes and regulators that could be used as biomarkers or potential therapeutic targets.
author2 Lee Kong Chian School of Medicine (LKCMedicine)
author_facet Lee Kong Chian School of Medicine (LKCMedicine)
Xie, Enrui
Shen, Xiaotao
Yeo, Yee Hui
Xing, Zixuan
Ebinger, Joseph E.
Duan, Yixuan
Zhang, Yue
Cheng, Susan
Ji, Fanpu
Deng, Jie
format Article
author Xie, Enrui
Shen, Xiaotao
Yeo, Yee Hui
Xing, Zixuan
Ebinger, Joseph E.
Duan, Yixuan
Zhang, Yue
Cheng, Susan
Ji, Fanpu
Deng, Jie
author_sort Xie, Enrui
title Exploring the underlying molecular mechanisms of acute myocardial infarction after SARS-CoV-2 infection
title_short Exploring the underlying molecular mechanisms of acute myocardial infarction after SARS-CoV-2 infection
title_full Exploring the underlying molecular mechanisms of acute myocardial infarction after SARS-CoV-2 infection
title_fullStr Exploring the underlying molecular mechanisms of acute myocardial infarction after SARS-CoV-2 infection
title_full_unstemmed Exploring the underlying molecular mechanisms of acute myocardial infarction after SARS-CoV-2 infection
title_sort exploring the underlying molecular mechanisms of acute myocardial infarction after sars-cov-2 infection
publishDate 2024
url https://hdl.handle.net/10356/181577
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