Heparanase Is a Putative Mediator of Endothelial Glycocalyx Damage in COVID-19 – A Proof-of-Concept Study
Carolin Christina Drost, Alexandros Rovas, Irina Osiaevi, Matthias Rauen, Johan van der Vlag, Baranca Buijsers, Rustem Salmenov, Alexander Lukasz, Hermann Pavenstädt, Wolfgang A. Linke, Philipp Kümpers
Source record
Source: Crossref
Published: Jun 10, 2022
DOI: 10.3389/fimmu.2022.916512
Open original source ↗Source abstract
Coronavirus disease 2019 (COVID-19) is a systemic disease associated with injury (thinning) of the endothelial glycocalyx (eGC), a protective layer on the vascular endothelium. The aim of this translational study was to investigate the role of the eGC-degrading enzyme heparanase (HPSE), which is known to play a central role in the destruction of the eGC in bacterial sepsis. Excess activity of HPSE in plasma from COVID-19 patients correlated with several markers of eGC damage and perfused boundary region (PBR, an inverse estimate of glycocalyx dimensions of vessels with a diameter 4-25 µm). In a series of translational experiments, we demonstrate that the changes in eGC thickness of cultured cells exposed to COVID-19 serum correlated closely with HPSE activity in concordant plasma samples (R = 0.82, P = 0.003). Inhibition of HPSE by a nonanticoagulant heparin fragment prevented eGC injury in response to COVID-19 serum, as shown by atomic force microscopy and immunofluorescence imaging. Our results suggest that the protective effect of heparin in COVID-19 may be due to an eGC-protective off-target effect.
Evidence graph
No public relationships recorded yet.
Integrity note: This page is a factual metadata record created by deterministic ingestion. It is not a claim that the work moves a mathematical frontier or has been independently verified.