Endothelial glycocalyx shields the interaction of SARS-CoV-2 spike protein with ACE2 receptors

Endothelial cells (ECs) play a crucial role in the development and propagation of the severe COVID-19 stage as well as multiorgan dysfunction. It remains, however, controversial whether COVID-19-induced endothelial injury is caused directly by the infection of ECs with SARS-CoV-2 or via indirect mec...

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Bibliographic Details
Published in:Scientific reports 2021-06, Vol.11 (1), p.12157-12157, Article 12157
Main Authors: Targosz-Korecka, Marta, Kubisiak, Agata, Kloska, Damian, Kopacz, Aleksandra, Grochot-Przeczek, Anna, Szymonski, Marek
Format: Article
Language:English
Subjects:
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ACE2
Angiotensin-converting enzyme 2
Coronaviruses
COVID-19
Endothelial cells
Humanities and Social Sciences
multidisciplinary
Proteins
Pulmonary arteries
Pulmonary artery
Science
Science (multidisciplinary)
Severe acute respiratory syndrome coronavirus 2
Spectroscopy
Spike protein
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Summary:Endothelial cells (ECs) play a crucial role in the development and propagation of the severe COVID-19 stage as well as multiorgan dysfunction. It remains, however, controversial whether COVID-19-induced endothelial injury is caused directly by the infection of ECs with SARS-CoV-2 or via indirect mechanisms. One of the major concerns is raised by the contradictory data supporting or denying the presence of ACE2, the SARS-CoV-2 binding receptor, on the EC surface. Here, we show that primary human pulmonary artery ECs possess ACE2 capable of interaction with the viral Spike protein (S-protein) and demonstrate the crucial role of the endothelial glycocalyx in the regulation of the S-protein binding to ACE2 on ECs. Using force spectroscopy method, we directly measured ACE2- and glycocalyx-dependent adhesive forces between S-protein and ECs and characterized the nanomechanical parameters of the cells exposed to S-protein. We revealed that the intact glycocalyx strongly binds S-protein but screens its interaction with ACE2. Reduction of glycocalyx layer exposes ACE2 receptors and promotes their interaction with S-protein. These results indicate that the susceptibility of ECs to COVID-19 infection may depend on the glycocalyx condition.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-021-91231-1