Department of Medicine D, Division of General Internal and Emergency Medicine, Nephrology, and Rheumatology, University Hospital Münster, Münster, Germany.
Department of Medicine A, Division of Hematology, Oncology, Hemostaseology and Pneumology, University Hospital Münster, Münster, Germany.
Front Immunol. 2022 Jun 10;13:916512. doi: 10.3389/fimmu.2022.916512. eCollection 2022.
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.
2019 年冠状病毒病（COVID-19）是一种与内皮糖萼（eGC）损伤（变薄）相关的全身性疾病，eGC 是血管内皮的保护层。本转化研究的目的是研究 eGC 降解酶肝素酶（HPSE）的作用，已知 HPSE 在细菌败血症中 eGC 破坏中起核心作用。COVID-19 患者血浆中 HPSE 的过度活性与 eGC 损伤和灌注边界区（PBR，直径为 4-25μm 的血管糖萼尺寸的倒数估计）的几个标志物相关。在一系列转化实验中，我们证明了暴露于 COVID-19 血清的培养细胞的 eGC 厚度变化与一致的血浆样本中的 HPSE 活性密切相关（R = 0.82，P = 0.003）。非抗凝肝素片段抑制 HPSE 可防止 COVID-19 血清引起的 eGC 损伤，这通过原子力显微镜和免疫荧光成像显示。我们的结果表明，肝素在 COVID-19 中的保护作用可能是由于 eGC 保护的脱靶效应。
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