Serum from COVID-19 patients promotes endothelial cell dysfunction through protease-activated receptor 2
© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG..
BACKGROUND: Endothelial dysfunction plays a central role in the pathophysiology of COVID-19 and is closely linked to the severity and mortality of the disease. The inflammatory response to SARS-CoV-2 infection can alter the capacity of the endothelium to regulate vascular tone, immune responses, and the balance between anti-thrombotic and pro-thrombotic properties. However, the specific endothelial pathways altered during COVID-19 still need to be fully understood.
OBJECTIVE: In this study, we sought to identify molecular changes in endothelial cells induced by circulating factors characteristic of COVID-19.
METHODS AND RESULTS: To this aim, we cultured endothelial cells with sera from patients with COVID-19 or non-COVID-19 pneumonia. Through transcriptomic analysis, we were able to identify a distinctive endothelial phenotype that is induced by sera from COVID-19 patients. We confirmed and expanded this observation in vitro by showing that COVID-19 serum alters functional properties of endothelial cells leading to increased apoptosis, loss of barrier integrity, and hypercoagulability. Furthermore, we demonstrated that these endothelial dysfunctions are mediated by protease-activated receptor 2 (PAR-2), as predicted by transcriptome network analysis validated by in vitro functional assays.
CONCLUSION: Our findings provide the rationale for further studies to evaluate whether targeting PAR-2 may be a clinically effective strategy to counteract endothelial dysfunction in COVID-19.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:73 |
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| Enthalten in: |
Inflammation research : official journal of the European Histamine Research Society ... [et al. - 73(2024), 1 vom: 09. Jan., Seite 117-130 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Vieceli Dalla Sega, Francesco [VerfasserIn] |
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| Links: |
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| Themen: |
COVID-19 |
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| Anmerkungen: |
Date Completed 10.01.2024 Date Revised 10.01.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1007/s00011-023-01823-y |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM366079727 |
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| 245 | 1 | 0 | |a Serum from COVID-19 patients promotes endothelial cell dysfunction through protease-activated receptor 2 |
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| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG. | ||
| 520 | |a BACKGROUND: Endothelial dysfunction plays a central role in the pathophysiology of COVID-19 and is closely linked to the severity and mortality of the disease. The inflammatory response to SARS-CoV-2 infection can alter the capacity of the endothelium to regulate vascular tone, immune responses, and the balance between anti-thrombotic and pro-thrombotic properties. However, the specific endothelial pathways altered during COVID-19 still need to be fully understood | ||
| 520 | |a OBJECTIVE: In this study, we sought to identify molecular changes in endothelial cells induced by circulating factors characteristic of COVID-19 | ||
| 520 | |a METHODS AND RESULTS: To this aim, we cultured endothelial cells with sera from patients with COVID-19 or non-COVID-19 pneumonia. Through transcriptomic analysis, we were able to identify a distinctive endothelial phenotype that is induced by sera from COVID-19 patients. We confirmed and expanded this observation in vitro by showing that COVID-19 serum alters functional properties of endothelial cells leading to increased apoptosis, loss of barrier integrity, and hypercoagulability. Furthermore, we demonstrated that these endothelial dysfunctions are mediated by protease-activated receptor 2 (PAR-2), as predicted by transcriptome network analysis validated by in vitro functional assays | ||
| 520 | |a CONCLUSION: Our findings provide the rationale for further studies to evaluate whether targeting PAR-2 may be a clinically effective strategy to counteract endothelial dysfunction in COVID-19 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a COVID-19 | |
| 650 | 4 | |a Coagulopathy | |
| 650 | 4 | |a Endothelial dysfunction | |
| 650 | 4 | |a PAR-2 | |
| 650 | 4 | |a Protease-activated receptor | |
| 650 | 4 | |a SARS-CoV-2 | |
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| 700 | 1 | |a Marracino, Luisa |e verfasserin |4 aut | |
| 700 | 1 | |a Severi, Paolo |e verfasserin |4 aut | |
| 700 | 1 | |a D'Accolti, Maria |e verfasserin |4 aut | |
| 700 | 1 | |a Soffritti, Irene |e verfasserin |4 aut | |
| 700 | 1 | |a Brambilla, Marta |e verfasserin |4 aut | |
| 700 | 1 | |a Camera, Marina |e verfasserin |4 aut | |
| 700 | 1 | |a Tremoli, Elena |e verfasserin |4 aut | |
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| 700 | 1 | |a Rizzo, Paola |e verfasserin |4 aut | |
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