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- Title
Serum from COVID-19 patients promotes endothelial cell dysfunction through protease-activated receptor 2.
- Authors
Vieceli Dalla Sega, Francesco; Fortini, Francesca; Licastro, Danilo; Monego, Simeone Dal; Degasperi, Margherita; Ascierto, Alessia; Marracino, Luisa; Severi, Paolo; D'Accolti, Maria; Soffritti, Irene; Brambilla, Marta; Camera, Marina; Tremoli, Elena; Contoli, Marco; Spadaro, Savino; Campo, Gianluca; Ferrari, Roberto; Caselli, Elisabetta; Rizzo, Paola
- Abstract
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.
- Subjects
PROTEASE-activated receptors; COVID-19; ENDOTHELIAL cells; COVID-19 pandemic; ENDOTHELIUM diseases; VASCULAR endothelium
- Publication
Inflammation Research, 2024, Vol 73, Issue 1, p117
- ISSN
1023-3830
- Publication type
Article
- DOI
10.1007/s00011-023-01823-y