Serum from COVID-19 patients promotes endothelial cell dysfunction through protease-activated receptor 2.

Autor: 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
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Zdroj: Inflammation Research; Jan2024, Vol. 73 Issue 1, p117-130, 14p
Abstrakt: 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. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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