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Uncovering common pathobiological processes between COVID‐19 and pulmonary arterial hypertension by integrating Omics data
Coronavirus disease 2019 (COVID‐19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), which led to the current pandemic. Many factors, including age and comorbidities, influence the severity and mortality of COVID‐19. SARS‐CoV‐2 infection can cause pulm...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9880519/ https://www.ncbi.nlm.nih.gov/pubmed/36721384 http://dx.doi.org/10.1002/pul2.12191 |
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author | Wang, Rui‐Sheng Loscalzo, Joseph |
author_facet | Wang, Rui‐Sheng Loscalzo, Joseph |
author_sort | Wang, Rui‐Sheng |
collection | PubMed |
description | Coronavirus disease 2019 (COVID‐19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), which led to the current pandemic. Many factors, including age and comorbidities, influence the severity and mortality of COVID‐19. SARS‐CoV‐2 infection can cause pulmonary vascular dysfunction. The COVID‐19 case‐fatality rate in patients with pulmonary arterial hypertension (PAH) is higher in comparison with the general population. In this study, we aimed to identify pathobiological processes common to COVID‐19 and PAH by utilizing the human protein–protein interactome and whole‐genome transcription data from peripheral blood mononuclear cells (PBMCs) and from lung tissue. We found that there are significantly more interactions between SARS‐CoV‐2 targets and PAH disease proteins than expected by chance, suggesting that the PAH disease module is in the neighborhood of SARS‐CoV‐2 targets in the human interactome. In addition, SARS‐CoV‐2 infection‐induced changes in gene expression significantly overlap with PAH‐induced gene expression changes in both tissues, indicating SARS‐CoV‐2 and PAH may share common transcriptional regulators. We identified many upregulated genes and downregulated genes common to COVID‐19 and PAH. Interestingly, we observed different co‐regulation patterns and dysfunctional signaling pathways in PBMCs versus lung tissue. Endophenotype enrichment analysis revealed that genes regulating fibrosis, inflammation, hypoxia, oxidative stress, immune response, and thromboembolism are significantly enriched in the COVID‐19‐PAH co‐expression modules. We examined the network proximity of the targets of repositioned drugs for COVID‐19 to the co‐expression modules in PBMCs and lung tissue, and identified 42 drugs that can be potentially used for COVID‐19 patients with PAH as a comorbidity. The uncovered common pathobiological pathways are crucial for discovering therapeutic targets and designing tailored treatments for COVID‐19 patients who also have PAH. |
format | Online Article Text |
id | pubmed-9880519 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-98805192023-01-30 Uncovering common pathobiological processes between COVID‐19 and pulmonary arterial hypertension by integrating Omics data Wang, Rui‐Sheng Loscalzo, Joseph Pulm Circ Research Articles Coronavirus disease 2019 (COVID‐19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), which led to the current pandemic. Many factors, including age and comorbidities, influence the severity and mortality of COVID‐19. SARS‐CoV‐2 infection can cause pulmonary vascular dysfunction. The COVID‐19 case‐fatality rate in patients with pulmonary arterial hypertension (PAH) is higher in comparison with the general population. In this study, we aimed to identify pathobiological processes common to COVID‐19 and PAH by utilizing the human protein–protein interactome and whole‐genome transcription data from peripheral blood mononuclear cells (PBMCs) and from lung tissue. We found that there are significantly more interactions between SARS‐CoV‐2 targets and PAH disease proteins than expected by chance, suggesting that the PAH disease module is in the neighborhood of SARS‐CoV‐2 targets in the human interactome. In addition, SARS‐CoV‐2 infection‐induced changes in gene expression significantly overlap with PAH‐induced gene expression changes in both tissues, indicating SARS‐CoV‐2 and PAH may share common transcriptional regulators. We identified many upregulated genes and downregulated genes common to COVID‐19 and PAH. Interestingly, we observed different co‐regulation patterns and dysfunctional signaling pathways in PBMCs versus lung tissue. Endophenotype enrichment analysis revealed that genes regulating fibrosis, inflammation, hypoxia, oxidative stress, immune response, and thromboembolism are significantly enriched in the COVID‐19‐PAH co‐expression modules. We examined the network proximity of the targets of repositioned drugs for COVID‐19 to the co‐expression modules in PBMCs and lung tissue, and identified 42 drugs that can be potentially used for COVID‐19 patients with PAH as a comorbidity. The uncovered common pathobiological pathways are crucial for discovering therapeutic targets and designing tailored treatments for COVID‐19 patients who also have PAH. John Wiley and Sons Inc. 2023-01-26 /pmc/articles/PMC9880519/ /pubmed/36721384 http://dx.doi.org/10.1002/pul2.12191 Text en © 2023 The Authors. Pulmonary Circulation published by John Wiley & Sons Ltd on behalf of Pulmonary Vascular Research Institute. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Research Articles Wang, Rui‐Sheng Loscalzo, Joseph Uncovering common pathobiological processes between COVID‐19 and pulmonary arterial hypertension by integrating Omics data |
title | Uncovering common pathobiological processes between COVID‐19 and pulmonary arterial hypertension by integrating Omics data |
title_full | Uncovering common pathobiological processes between COVID‐19 and pulmonary arterial hypertension by integrating Omics data |
title_fullStr | Uncovering common pathobiological processes between COVID‐19 and pulmonary arterial hypertension by integrating Omics data |
title_full_unstemmed | Uncovering common pathobiological processes between COVID‐19 and pulmonary arterial hypertension by integrating Omics data |
title_short | Uncovering common pathobiological processes between COVID‐19 and pulmonary arterial hypertension by integrating Omics data |
title_sort | uncovering common pathobiological processes between covid‐19 and pulmonary arterial hypertension by integrating omics data |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9880519/ https://www.ncbi.nlm.nih.gov/pubmed/36721384 http://dx.doi.org/10.1002/pul2.12191 |
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