ArticleFrontiers in immunology2022
Heparanase Is a Putative Mediator of Endothelial Glycocalyx Damage in COVID-19 - A Proof-of-Concept Study.
Article in Frontiers in immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 15 citations in OpenAlex.
- Plasma Heparan Sulfate Structural Variation and Phenotypic Heterogeneity in Pediatric Acute Respiratory Distress Syndrome.Research square · 2026Article
- Role of neutrophils in regulating vascular permeability in inflammatory and autoimmune diseases.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Endothelial Surface Glycocalyx in Vascular Functions and Diseases.Advances in experimental medicine and biology · 2026Review
- Early systemic heparin exposure is associated with lower mortality, reduced disseminated intravascular coagulation, and fewer thrombotic complications in septic shock.Frontiers in medicine · 2026Article
- Challenging the notion of endothelial infection by SARS-CoV-2: insights from the current scientific evidence.Frontiers in immunology · 2025Article
- Interleukin-6 drives endothelial glycocalyx damage in COVID-19 and bacterial sepsis.Angiogenesis · 2024Observational
- Aprotinin (I): Understanding the Role of Host Proteases in COVID-19 and the Importance of Pharmacologically Regulating Their Function.International journal of molecular sciences · 2024Review
- Aprotinin (II): Inhalational Administration for the Treatment of COVID-19 and Other Viral Conditions.International journal of molecular sciences · 2024Review
- The Role of Heparin in Postural Orthostatic Tachycardia Syndrome and Other Post-Acute Sequelae of COVID-19.Journal of clinical medicine · 2024Review
- Endothelial dysfunction in COVID-19: an overview of evidence, biomarkers, mechanisms and potential therapies.Acta pharmacologica Sinica · 2023Review
- Longitudinal Assessment of Plasma Syndecan-1 Predicts 60-Day Mortality in Patients with COVID-19.Journal of clinical medicine · 2023Article
- SARS-CoV-2 and Endothelial Cells: Vascular Changes, Intussusceptive Microvascular Growth and Novel Therapeutic Windows.Biomedicines · 2022Review
- The Potential Impact of Heparanase Activity and Endothelial Damage in COVID-19 Disease.Journal of clinical medicine · 2022Article
- Alveolar glycocalyces during health and critical illness.Proteoglycan researchArticle
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.