ArticleScientific reports2019
Heparanase-2 protects from LPS-mediated endothelial injury by inhibiting TLR4 signalling.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 60 citations in OpenAlex.
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- Intrapericardially injected hydrogel loaded with stromal cell secretome microparticles improves post-infarction myocardial repair in pigs.European heart journal · 2026Article
- Heparanase 2 (Hpa2) protects the exocrine pancreas from damages of Western diet and pancreatic cancer.International journal of biological sciences · 2026Article
- Knowledge gaps in extracorporeal blood purification: what would be required for its successful application in septic shock?Intensive care medicine experimental · 2025Review
- Heparanase 2 Modulates Vascular Permeability via Heparan Sulfate-Dependent Growth Factor Signaling.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- 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
- Review
- Endothelial Glycocalyx Turnover in Vascular Health and Disease: Rethinking Endothelial Dysfunction.Annual review of biochemistry · 2025Review
- Lasmiditan induces mitochondrial biogenesis in primary mouse renal peritubular endothelial cells and augments wound healing and tubular network formation.American journal of physiology. Cell physiology · 2025Article
- Current understanding of heparanase 2 regulation, a non-heparanase.Biochemical Society transactions · 2025Article
- Decoding interaction between mitochondria and endoplasmic reticulum in ischemic myocardial injury: targeting natural medicines.Frontiers in pharmacology · 2025Review
- Tumor- and host-derived heparanase-2 (Hpa2) attenuates tumorigenicity: role of Hpa2 in macrophage polarization and BRD7 nuclear localization.Cell death & disease · 2024Article
- Article
- Endothelial cell dynamics in sepsis-induced acute lung injury and acute respiratory distress syndrome: pathogenesis and therapeutic implications.Cell communication and signaling : CCS · 2024Review
- Glycocalyx Disruption Triggers Human Monocyte Activation in Acute Heart Failure Syndromes.Cardiovascular drugs and therapy · 2024Article
- Nuclear localization of heparanase 2 (Hpa2) attenuates breast carcinoma growth and metastasis.Cell death & disease · 2024Article
- Vasculature-on-a-chip technologies as platforms for advanced studies of bacterial infections.Biomicrofluidics · 2024Review
- Heparanase inhibitor improves clinical study in patients with septic cardiomyopathy.Frontiers in medicine · 2024Article
- Role of heparanase in sepsis‑related acute kidney injury (Review).Experimental and therapeutic medicine · 2023Review
- Heparanase 2 (Hpa2)- a new player essential for pancreatic acinar cell differentiation.Cell death & disease · 2023Article
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The endothelial glycocalyx and its regulated shedding are important to vascular health. Endo-β-D-glucuronidase heparanase-1 (HPSE1) is the only enzyme that can shed heparan sulfate. However, the mechanisms are not well understood. We show that HPSE1 activity aggravated Toll-like receptor 4 (TLR4)-mediated response of endothelial cells to LPS. On the contrary, overexpression of its endogenous inhibitor, heparanase-2 (HPSE2) was protective. The microfluidic chip flow model confirmed that HPSE2 prevented heparan sulfate shedding by HPSE1. Furthermore, heparan sulfate did not interfere with cluster of differentiation-14 (CD14)-dependent LPS binding, but instead reduced the presentation of the LPS to TLR4. HPSE2 reduced LPS-mediated TLR4 activation, subsequent cell signalling, and cytokine expression. HPSE2-overexpressing endothelial cells remained protected against LPS-mediated loss of cell-cell contacts. In vivo, expression of HPSE2 in plasma and kidney medullary capillaries was decreased in mouse sepsis model. We next applied purified HPSE2 in mice and observed decreases in TNFα and IL-6 plasma concentrations after intravenous LPS injections. Our data demonstrate the important role of heparan sulfate and the glycocalyx in endothelial cell activation and suggest a protective role of HPSE2 in microvascular inflammation. HPSE2 offers new options for protection against HPSE1-mediated endothelial damage and preventing microvascular disease.
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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 OpenQuestion graph.