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PROTEOMIC PROFILE OF PROCOAGULANT EXTRACELLULAR VESICLES REFLECTS COMPLEMENT SYSTEM ACTIVATION AND PLATELET HYPERREACTIVITY OF PATIENTS WITH SEVERE COVID-19
Vesículas extracelulares
Proteoma
LC-MS/MS
Plaquetas
Fatores complementares
Fator tecidual
LC-MS/MS
Proteome
SARS-CoV-2
Platelets
Complement factors
Tissue factor
Author
Affilliation
Abstract
Background: Extracellular vesicles (EVs) are a valuable source of biomarkers and display
the pathophysiological status of various diseases. In COVID-19, EVs have been explored
in several studies for their ability to reflect molecular changes caused by SARS-CoV-2.
Here we provide insights into the roles of EVs in pathological processes associated with
the progression and severity of COVID-19.
Methods: In this study, we used a label-free shotgun proteomic approach to identify and
quantify alterations in EV protein abundance in severe COVID-19 patients. We isolated
plasma extracellular vesicles from healthy donors and patients with severe COVID-19 by
size exclusion chromatography (SEC). Then, flow cytometry was performed to assess the
origin of EVs and to investigate the presence of circulating procoagulant EVs in COVID-19
patients. A total protein extraction was performed, and samples were analyzed by nLCMS/
MS in a Q-Exactive HF-X. Finally, computational analysis was applied to signify
biological processes related to disease pathogenesis.
Results: We report significant changes in the proteome of EVs from patients with severe
COVID-19. Flow cytometry experiments indicated an increase in total circulating EVs and
with tissue factor (TF) dependent procoagulant activity. Differentially expressed proteins in
the disease groups were associated with complement and coagulation cascades, platelet
degranulation, and acute inflammatory response. Conclusions: The proteomic data reinforce the changes in the proteome of extracellular
vesicles from patients infected with SARS-CoV-2 and suggest a role for EVs in severe
COVID-19.
Keywords in Portuguese
SARS-CoV-2Vesículas extracelulares
Proteoma
LC-MS/MS
Plaquetas
Fatores complementares
Fator tecidual
Keywords
Extracellular vesiclesLC-MS/MS
Proteome
SARS-CoV-2
Platelets
Complement factors
Tissue factor
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