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.
【저자키워드】 COVID-19, heparin, endothelial glycocalyx (EG), heparanase (HPSE), videomicroscopy., 【초록키워드】 Coronavirus disease 2019, inhibition, serum, Microscopy, plasma, immunofluorescence, disease, Bacterial sepsis, protective effect, Protective, marker, Injury, COVID-19 patient, Vascular endothelium, endothelial, enzyme, excess, dimension, vessel, plasma sample, shown, cultured cell, atomic, changes in, correlated, prevented, experiments, translational, HPSE, 【제목키워드】 glycocalyx, mediator, Heparanase, damage,