| Autor: |
Abdullah O. Khan, Max Crispin, Adam F. Cunningham, Maddy L. Newby, Martina Colicchia, Zania Stamataki, Richter Ag, Matthew Pugh, Joel D. Allen, Joshua H. Bourne, Gemma M J Taylor, Youd E, Jasmeet S. Reyat, Julie Rayes, Paul Murray |
| Rok vydání: |
2021 |
| Předmět: |
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| Popis: |
ObjectiveThrombotic 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 ResultsWe 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.ConclusionsOur 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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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