ArticleDiabetologia2011
Reactive oxygen species mediate high glucose-induced heparanase-1 production and heparan sulphate proteoglycan degradation in human and rat endothelial cells: a potential role in the pathogenesis of atherosclerosis.
Article in Diabetologia, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 55 citations in OpenAlex.
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- The Role of Endothelial Glycocalyx in the Pathophysiology of Chronic Kidney Disease and Hypertension: From Molecular Mechanisms to Clinical Biomarkers.Life (Basel, Switzerland) · 2026Review
- Mesenchymal stromal cell secretome reduces lung injury and thrombo-inflammation induced by SARS-CoV-2 spike protein.Stem cell research & therapy · 2025Article
- Identification of Neutrophil Extracellular Trap-Related Biomarkers in Diabetic Foot Ulcers Based on Bioinformatics.Journal of inflammation research · 2025Article
- Endothelial glycocalyx in retina, hyperglycemia, and diabetic retinopathy.American journal of physiology. Cell physiology · 2023Review
- Review
- Effect of high glucose on glycosaminoglycans in cultured retinal endothelial cells and rat retina.Glycobiology · 2022Article
- Resveratrol Decreases the Invasion Potential of Gastric Cancer Cells.Molecules (Basel, Switzerland) · 2022Article
- Heparanase as active player in endothelial glycocalyx remodeling.Matrix biology plus · 2022Article
- Integrative biology of extracellular vesicles in diabetes mellitus and diabetic complications.Theranostics · 2022Review
- The Heparanase Regulatory Network in Health and Disease.International journal of molecular sciences · 2021Review
- Cardiovascular Benefits from Gliflozins: Effects on Endothelial Function.Biomedicines · 2021Review
- Inhibition of heparanase protects against pancreatic beta cell death in streptozotocin-induced diabetic mice via reducing intra-islet inflammatory cell infiltration.British journal of pharmacology · 2020Article
- The Beneficial Effect of HES on Vascular Permeability and Its Relationship With Endothelial Glycocalyx and Intercellular Junction After Hemorrhagic Shock.Frontiers in pharmacology · 2020Article
- Roles of Endovascular Calyx Related Enzymes in Endothelial Dysfunction and Diabetic Vascular Complications.Frontiers in pharmacology · 2020Article
- Acacetin Protects Against High Glucose-Induced Endothelial Cells Injury by Preserving Mitochondrial Function via Activating Sirt1/Sirt3/AMPK Signals.Frontiers in pharmacology · 2020Article
- Empagliflozin restores the integrity of the endothelial glycocalyx in vitro.Molecular and cellular biochemistry · 2019Article
- Heparanase upregulation from adipocyte associates with inflammation and endothelial injury in diabetic condition.BMC proceedings · 2019Article
- Heparanase augments insulin receptor signaling in breast carcinoma.Oncotarget · 2017Article
- Functional role of inorganic trace elements in angiogenesis part III: (Ti, Li, Ce, As, Hg, Va, Nb and Pb).Critical reviews in oncology/hematology · 2016Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisThe content of heparan sulphate is reduced in the endothelium under hyperglycaemic conditions and may contribute to the pathogenesis of atherosclerosis. Heparanase-1 (HPR1) specifically degrades heparan sulphate proteoglycans. We therefore sought to determine whether: (1) heparan sulphate reduction in endothelial cells is due to increased HPR1 production through increased reactive oxygen species (ROS) production; and (2) HPR1 production is increased in vivo in endothelial cells under hyperglycaemic and/or atherosclerotic conditions.
methodsHPR1 mRNA and protein levels in endothelial cells were analysed by RT-PCR and Western blot or HPR1 enzymatic activity assay, respectively. Cell surface heparan sulphate levels were analysed by FACS. HPR1 in the artery from control rats and a rat model of diabetes, and from patients under hyperglycaemic and/or atherosclerotic conditions was immunohistochemically examined.
resultsHigh-glucose-induced HPR1 production and heparan sulphate degradation in three human endothelial cell lines, both of which were blocked by ROS scavengers, glutathione and N-acetylcysteine. Exogenous H(2)O(2) induced HPR1 production, subsequently leading to decreased cell surface heparan sulphate levels. HPR1 content was significantly increased in endothelial cells in the arterial walls of a rat model of diabetes. Clinical studies revealed that HPR1 production was increased in endothelial cells under hyperglycaemic conditions, and in endothelial cells and macrophages in atherosclerotic lesions. CONCLUSIONS/
interpretationHyperglycaemia induces HPR1 production and heparan sulphate degradation in endothelial cells through ROS. HPR1 production is increased in endothelial cells from a rat model of diabetes, and in macrophages in the atherosclerotic lesions of diabetic and non-diabetic patients. Increased HPR1 production may contribute to the pathogenesis and progression of atherosclerosis.
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