ArticleJournal of thrombosis and haemostasis : JTH2021
Heparanase expression and activity are increased in platelets during clinical sepsis.
Article in Journal of thrombosis and haemostasis : JTH, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
What it found
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The trial behind it
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Pooled it
- Heparanase inhibition leads to improvement in patients with acute gastrointestinal injuries induced by sepsis.World journal of gastroenterology · 2023Trial
- Sepsis-induced endothelial glycocalyx disruption and remodeling: an ultrastructural study in mice.Intensive care medicine experimental · 2026Article
- Heme and hemozoin induce platelet cell death through UPR-induced apoptosis and ferroptosis in vivax malaria.Blood advances · 2026Article
- Anticoagulants beyond coagulation: repurposing heparin to mitigate immunothrombosis and inflammatory cascades in sepsis.Frontiers in pharmacology · 2026Review
- Gastrointestinal axis in post-traumatic sepsis: from molecular mechanisms to translational perspectives.Frontiers in immunology · 2026Review
- Age-related differences in circulating heparanase-1 activity in sepsis and correlation with systemic vascular endotheliopathy.Frontiers in medicine · 2026Article
- Targeting PANoptosis: a promising therapeutic strategy for ALI/ARDS.Apoptosis : an international journal on programmed cell death · 2025Review
- Explainable AI unravels sepsis heterogeneity via coagulation-inflammation profiles for prognosis and stratification.Nature communications · 2025Observational
- The Pathophysiological Functions of Heparanases: From Evolution, Structural and Tissue-Specific Perspectives.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Review
- Lactylation of Histone H3k18 and Egr1 Promotes Endothelial Glycocalyx Degradation in Sepsis-Induced Acute Lung Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Glycosaminoglycans: Participants in Microvascular Coagulation of Sepsis.Thrombosis and haemostasis · 2024Review
- Review
- Deciphering Abnormal Platelet Subpopulations in COVID-19, Sepsis and Systemic Lupus Erythematosus through Machine Learning and Single-Cell Transcriptomics.International journal of molecular sciences · 2024Article
- Platelets and Thrombotic Antiphospholipid Syndrome.Journal of clinical medicine · 2024Review
- Relationship between low molecular weight heparin calcium therapy and prognosis in severe acute kidney injury in sepsis: Mendelian randomized analysis and retrospective study.Frontiers in pharmacology · 2024Article
- Sepsis-Induced Endothelial Dysfunction: Permeability and Regulated Cell Death.Journal of inflammation research · 2024Review
- Heparin, Heparan Sulphate and Sepsis: Potential New Options for Treatment.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Signaling network analysis reveals fostamatinib as a potential drug to control platelet hyperactivation during SARS-CoV-2 infection.Frontiers in immunology · 2023Article
- Article
Corrections and comments
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Authors and funding
19 authors at 5 institutions in 3 countries.
Funding
Abstract
backgroundHeparanase (HPSE) is the only known mammalian enzyme that can degrade heparan sulfate. Heparan sulfate proteoglycans are essential components of the glycocalyx, and maintain physiological barriers between the blood and endothelial cells. HPSE increases during sepsis, which contributes to injurious glyocalyx degradation, loss of endothelial barrier function, and mortality.
objectivesAs platelets are one of the most abundant cellular sources of HPSE, we sought to determine whether HPSE expression and activity increases in human platelets during clinical sepsis. We also examined associations between platelet HPSE expression and clinical outcomes. PATIENTS/
methodsExpression and activity of HPSE was determined in platelets isolated from septic patients (n = 59) and, for comparison, sex-matched healthy donors (n = 46) using complementary transcriptomic, proteomic, and functional enzymatic assays. Septic patients were followed for the primary outcome of mortality, and clinical data were captured prospectively for septic patients.
resultsThe mRNA expression of HPSE was significantly increased in platelets isolated from septic patients. Ribosomal footprint profiling, followed by [S35] methionine labeling assays, demonstrated that HPSE mRNA translation and HPSE protein synthesis were significantly upregulated in platelets during sepsis. While both the pro- and active forms of HPSE protein increased in platelets during sepsis, only the active form of HPSE protein significantly correlated with sepsis-associated mortality. Consistent with transcriptomic and proteomic upregulation, HPSE enzymatic activity was also increased in platelets during sepsis.
conclusionsDuring clinical sepsis HPSE, translation, and enzymatic activity are increased in platelets. Increased expression of the active form of HPSE protein is associated with sepsis-associated mortality.
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