ArticleArteriosclerosis, thrombosis, and vascular biology2013
Macrophage activation by heparanase is mediated by TLR-2 and TLR-4 and associates with plaque progression.
Article in Arteriosclerosis, thrombosis, and vascular biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
What it found
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Who cites it
74 citing papers in PubMed, 128 citations in OpenAlex.
- Heparanase inhibition leads to improvement in patients with acute gastrointestinal injuries induced by sepsis.World journal of gastroenterology · 2023Trial
- Review
- Heparanase gene deficiency suppresses atherosclerosis progression and enhances plaque stability in apolipoprotein E gene knockout mice with diabetes.Clinical science (London, England : 1979) · 2026Article
- Heparanase, Endothelial Dysfunction, and Cardiovascular Risk: The Emerging Role of Vitamin D.ACS pharmacology & translational science · 2026Review
- The emerging role of heparanase in cardiovascular diseases: Pathophysiology, clinical outcomes, and therapeutic perspectives.Journal of thrombosis and thrombolysis · 2026Review
- Plasma Heparan Sulfate Structural Variation and Phenotypic Heterogeneity in Pediatric Acute Respiratory Distress Syndrome.Research square · 2026Article
- Molecular Pathways Driving Corneal Neovascularization in Herpes Simplex Keratitis.Pathogens (Basel, Switzerland) · 2026Review
- 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
- Glucocorticoid-Mediated Extracellular Matrix Regulation: Implications for Precision Therapy.Biomedicines · 2025Review
- Tumor- and host-derived heparanase-2 (Hpa2) attenuates tumorigenicity: role of Hpa2 in macrophage polarization and BRD7 nuclear localization.Cell death & disease · 2024Article
- The Uptake of Heparanase into Mast Cells Is Regulated by Its Enzymatic Activity to Degrade Heparan Sulfate.International journal of molecular sciences · 2024Article
- A New Synthesized Dicarboxylated Oxy-Heparin Efficiently Attenuates Tumor Growth and Metastasis.Cells · 2024Article
- High temperature influences DNA methylation and transcriptional profiles in sea urchins (Strongylocentrotus intermedius).BMC genomics · 2023Article
- Heparanase-A single protein with multiple enzymatic and nonenzymatic functions.Proteoglycan research · 2023Review
- Role of heparanase in pulmonary hypertension.Frontiers in pharmacology · 2023Review
- Flow-Induced Secretion of Endothelial Heparanase Regulates Cardiac Lipoprotein Lipase and Changes Following Diabetes.Journal of the American Heart Association · 2022Article
- Review
- Sulfated Hyaluronan Binds to Heparanase and Blocks Its Enzymatic and Cellular Actions in Carcinoma Cells.International journal of molecular sciences · 2022Article
- Heparanase as active player in endothelial glycocalyx remodeling.Matrix biology plus · 2022Article
- Targeting the "sweet spot" in septic shock - A perspective on the endothelial glycocalyx regulating proteins Heparanase-1 and -2.Matrix biology plus · 2021Review
14 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors at 1 institution in 1 country.
Funding
Abstract
objectiveFactors and mechanisms that activate macrophages in atherosclerotic plaques are incompletely understood. We examined the capacity of heparanase to activate macrophages. METHODS AND
resultsHighly purified heparanase was added to mouse peritoneal macrophages and macrophage-like J774 cells, and the levels of tumor necrosis factor-α, matrix metalloproteinase-9, interlukin-1, and monocyte chemotactic protein-1 were evaluated by ELISA. Gene expression was determined by RT-PCR. Cells collected from Toll-like receptor-2 and Toll-like receptor-4 knockout mice were evaluated similarly. Heparanase levels in the plasma of patients with acute myocardial infarction, stable angina, and healthy subjects were determined by ELISA. Immunohistochemistry was applied to detect the expression of heparanase in control specimens and specimens of patients with stable angina or acute myocardial infarction. Addition or overexpression of heparanase variants resulted in marked increase in tumor necrosis factor-α, matrix metalloproteinase-9, interlukin-1, and monocyte chemotactic protein-1 levels. Mouse peritoneal macrophages harvested from Toll-like receptor-2 or Toll-like receptor-4 knockout mice were not activated by heparanase. Plasma heparanase level was higher in patients with acute myocardial infarction, compared with patients with stable angina and healthy subjects. Pathologic coronary specimens obtained from vulnerable plaques showed increased heparanase staining compared with specimens of stable plaque and controls.
conclusionsHeparanase activates macrophages, resulting in marked induction of cytokine expression associated with plaque progression toward vulnerability.
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