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Stimulation of vascular organoids with SARS-CoV-2 antigens increases endothelial permeability and regulates vasculopathy (preprint)
medrxiv; 2021.
Preprint
in English
| medRxiv | ID: ppzbmed-10.1101.2021.04.25.21255890
ABSTRACT
Objective Thrombotic complications and vasculopathy have been extensively associated with severe COVID-19 infection, however the mechanisms by which endotheliitis is induced remain poorly understood. Here we investigate vascular permeability in the context of SARS-CoV-2-mediated endotheliitis in patient samples and a vascular organoid model. Methods and Results We report the presence of the Spike glycoprotein in pericytes associated with pericyte activation and increased endothelial permeability in post-mortem COVID-19 lung autopsies. A pronounced decrease in the expression of the adhesion molecule VE-cadherin is observed in patients with thrombotic complications. Interestingly, fibrin-rich thrombi did not contain platelets, did not colocalize with tissue factor and have heterogenous levels of Von Willebrand factor, suggesting a biomarker-guided therapy might be required to target thrombosis in severe patients. Using a 3D vascular organoid model, we observe that ACE2 is primarily expressed in pericytes adjacent to vascular networks, consistent with patient data, indicating a preferential uptake of the S glycoprotein by these cells. Exposure of vascular organoids to SARS-CoV-2 or its antigens, recombinant trimeric Spike glycoprotein and Nucleocapsid protein, reduced endothelial cell and pericyte viability as well as CD144 expression with no additive effect upon endothelial activation via IL-1β. Conclusions Our data suggest that pericyte uptake of SARS-CoV-2 or Spike glycoprotein contributes to vasculopathy by altering endothelial permeability increasing the risk of thrombotic complications.
Full text:
Available
Collection:
Preprints
Database:
medRxiv
Main subject:
Thrombosis
/
Von Willebrand Diseases
/
Nevus, Sebaceous of Jadassohn
/
Susac Syndrome
/
COVID-19
Language:
English
Year:
2021
Document Type:
Preprint
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