tetano
Editor, Senior Moderator
Front Immunol
. 2022 Jun 10;13:916512.
doi: 10.3389/fimmu.2022.916512. eCollection 2022.
Heparanase Is a Putative Mediator of Endothelial Glycocalyx Damage in COVID-19 - A Proof-of-Concept Study
Carolin Christina Drost[SUP] 1 [/SUP], Alexandros Rovas[SUP] 1 [/SUP], Irina Osiaevi[SUP] 2 [/SUP], Matthias Rauen[SUP] 1 [/SUP], Johan van der Vlag[SUP] 3 [/SUP], Baranca Buijsers[SUP] 3 [/SUP], Rustem Salmenov[SUP] 3 [/SUP], Alexander Lukasz[SUP] 1 [/SUP], Hermann Pavenstädt[SUP] 1 [/SUP], Wolfgang A Linke[SUP] 4 [/SUP], Philipp Kümpers[SUP] 1 [/SUP]
Affiliations
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.
Keywords: COVID-19; endothelial glycocalyx (EG); heparanase (HPSE); heparin; videomicroscopy.
. 2022 Jun 10;13:916512.
doi: 10.3389/fimmu.2022.916512. eCollection 2022.
Heparanase Is a Putative Mediator of Endothelial Glycocalyx Damage in COVID-19 - A Proof-of-Concept Study
Carolin Christina Drost[SUP] 1 [/SUP], Alexandros Rovas[SUP] 1 [/SUP], Irina Osiaevi[SUP] 2 [/SUP], Matthias Rauen[SUP] 1 [/SUP], Johan van der Vlag[SUP] 3 [/SUP], Baranca Buijsers[SUP] 3 [/SUP], Rustem Salmenov[SUP] 3 [/SUP], Alexander Lukasz[SUP] 1 [/SUP], Hermann Pavenstädt[SUP] 1 [/SUP], Wolfgang A Linke[SUP] 4 [/SUP], Philipp Kümpers[SUP] 1 [/SUP]
Affiliations
- PMID: 35757776
- PMCID: PMC9226442
- DOI: 10.3389/fimmu.2022.916512
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.
Keywords: COVID-19; endothelial glycocalyx (EG); heparanase (HPSE); heparin; videomicroscopy.