Landscape of molecular crosstalk between SARS-CoV-2 infection and cardiovascular diseases: emphasis on mitochondrial dysfunction and immune-inflammation

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Abstract

Background

SARS-CoV-2, the pathogen of COVID-19, is a worldwide threat to human health and causes a long-term burden on the cardiovascular system. Individuals with pre-existing cardiovascular diseases are at higher risk for SARS-CoV-2 infection and tend to have a worse prognosis. However, the relevance and pathogenic mechanisms between COVID-19 and cardiovascular diseases are not yet completely comprehended.

Methods

Common differentially expressed genes (DEGs) were obtained in datasets of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) infected with SARS-CoV-2 and myocardial tissues from heart failure patients. Further GO and KEGG pathway analysis, protein–protein interaction (PPI) network construction, hub genes identification, immune microenvironment analysis, and drug candidate predication were performed. Then, an isoproterenol-stimulated myocardial hypertrophy cell model and a transverse aortic constriction-induced mouse heart failure model were employed to validate the expression of hub genes.

Results

A total of 315 up-regulated and 78 down-regulated common DEGs were identified. Functional enrichment analysis revealed mitochondrial metabolic disorders and extensive immune inflammation as the most prominent shared features of COVID-19 and cardiovascular diseases. Then, hub DEGs, as well as hub immune-related and mitochondria-related DEGs, were screened. Additionally, nine potential therapeutic agents for COVID-19-related cardiovascular diseases were proposed. Furthermore, the expression patterns of most of the hub genes related to cardiovascular diseases in the validation dataset along with cellular and mouse myocardial damage models, were consistent with the findings of bioinformatics analysis.

Conclusions

The study unveiled the molecular networks and signaling pathways connecting COVID-19 and cardiovascular diseases, which may provide novel targets for intervention of COVID-19-related cardiovascular diseases.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12967-023-04787-z.

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Imbalanced Host Response to SARS-CoV-2 Drives Development of COVID-19

Daniel Blanco-Melo, Benjamin E. Nilsson-Payant, Wen-Chun Liu … (2021)

Summary Viral pandemics, such as the one caused by SARS-CoV-2, pose an imminent threat to humanity. Because of its recent emergence, there is a paucity of information regarding viral behavior and host response following SARS-CoV-2 infection. Here we offer an in-depth analysis of the transcriptional response to SARS-CoV-2 compared with other respiratory viruses. Cell and animal models of SARS-CoV-2 infection, in addition to transcriptional and serum profiling of COVID-19 patients, consistently revealed a unique and inappropriate inflammatory response. This response is defined by low levels of type I and III interferons juxtaposed to elevated chemokines and high expression of IL-6. We propose that reduced innate antiviral defenses coupled with exuberant inflammatory cytokine production are the defining and driving features of COVID-19.

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Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients

Jérôme Hadjadj, Nader Yatim, Laura Barnabei … (2020)

Coronavirus disease 2019 (COVID-19) is characterized by distinct patterns of disease progression suggesting diverse host immune responses. We performed an integrated immune analysis on a cohort of 50 COVID-19 patients with various disease severity. A unique phenotype was observed in severe and critical patients, consisting of a highly impaired interferon (IFN) type I response (characterized by no IFN-β and low IFN-α production and activity), associated with a persistent blood viral load and an exacerbated inflammatory response. Inflammation was partially driven by the transcriptional factor NF-κB and characterized by increased tumor necrosis factor (TNF)-α and interleukin (IL)-6 production and signaling. These data suggest that type-I IFN deficiency in the blood could be a hallmark of severe COVID-19 and provide a rationale for combined therapeutic approaches.

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GEOquery: a bridge between the Gene Expression Omnibus (GEO) and BioConductor.

Sean Davis, Paul S. Meltzer (2007)

Microarray technology has become a standard molecular biology tool. Experimental data have been generated on a huge number of organisms, tissue types, treatment conditions and disease states. The Gene Expression Omnibus (Barrett et al., 2005), developed by the National Center for Bioinformatics (NCBI) at the National Institutes of Health is a repository of nearly 140,000 gene expression experiments. The BioConductor project (Gentleman et al., 2004) is an open-source and open-development software project built in the R statistical programming environment (R Development core Team, 2005) for the analysis and comprehension of genomic data. The tools contained in the BioConductor project represent many state-of-the-art methods for the analysis of microarray and genomics data. We have developed a software tool that allows access to the wealth of information within GEO directly from BioConductor, eliminating many the formatting and parsing problems that have made such analyses labor-intensive in the past. The software, called GEOquery, effectively establishes a bridge between GEO and BioConductor. Easy access to GEO data from BioConductor will likely lead to new analyses of GEO data using novel and rigorous statistical and bioinformatic tools. Facilitating analyses and meta-analyses of microarray data will increase the efficiency with which biologically important conclusions can be drawn from published genomic data. GEOquery is available as part of the BioConductor project.

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Author and article information

Contributors

Zhenya Shen: uuzyshen@aliyun.com

Journal

Journal ID (nlm-ta): J Transl Med

Journal ID (iso-abbrev): J Transl Med

Title: Journal of Translational Medicine

Publisher: BioMed Central (London )

ISSN (Electronic): 1479-5876

Publication date (Electronic): 16 December 2023

Publication date PMC-release: 16 December 2023

Publication date Collection: 2023

Volume: 21

Electronic Location Identifier: 915

Affiliations

GRID grid.263761.7, ISNI 0000 0001 0198 0694, Department of Cardiovascular Surgery of the First Affiliated Hospital and Institute for Cardiovascular Science, Suzhou Medical College, , Soochow University, ; Suzhou, 215006 China

Article

Publisher ID: 4787

DOI: 10.1186/s12967-023-04787-z

PMC ID: 10725609

PubMed ID: 38104081

SO-VID: a58e7a58-9651-453e-bac2-d5c6b9505a85

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 17 July 2023

Date accepted : 6 December 2023

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;

Award ID: No. 92168203

Award Recipient : Zhenya Shen

Funded by: Jiangsu Cardiovascular Medicine Innovation Center

Award ID: CXZX202210

Award Recipient : Zhenya Shen

Funded by: Science Foundation of the First Affiliated Hospital of Soochow University

Award ID: BXQN202223

Award Recipient : Shiyu Dai

Custom metadata

ScienceOpen disciplines: Medicine

Keywords: sars-cov-2,covid-19,cardiovascular diseases,mitochondria,immune,inflammation

Data availability:

ScienceOpen disciplines: Medicine

Keywords: sars-cov-2, covid-19, cardiovascular diseases, mitochondria, immune, inflammation

Landscape of molecular crosstalk between SARS-CoV-2 infection and cardiovascular diseases: emphasis on mitochondrial dysfunction and immune-inflammation

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Abstract

Background

Methods

Results

Conclusions

Supplementary Information

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Novel Coronavirus Disease COVID-19

Most cited references 103

Imbalanced Host Response to SARS-CoV-2 Drives Development of COVID-19

Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients

GEOquery: a bridge between the Gene Expression Omnibus (GEO) and BioConductor.

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