Heparanase in health and disease: The neglected housekeeper of the cell?

  • Jun Shu
    Department of Medicine, Albert Einstein College of Medicine, New York, NY, USA
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  • Gaetano Santulli
    Corresponding author.
    Department of Medicine and Department of Molecular Pharmacology, The Wilf Family Cardiovascular Research Institute, New York, NY, USA
    “The Norman Fleischer Institute for Diabetes and Metabolism”, Einstein-Sinai Diabetes Research Center, Albert Einstein College of Medicine, Montefiore University Hospital, New York, NY, USA
    Department of Biomedical Advanced Sciences, “Federico II” University, Naples, Italy
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      The membrane of most cells in the body is surrounded by a dynamically regulated, highly-hydrated fibrous meshwork of carbohydrates, known as pericellular matrix or glycocalyx. Its main constituents are several glycoconjugates (see nomenclature and definitions in Box 1), including glycolipids, the polysaccharide heparan sulfate (HS) linked to proteoglycan core proteins (e.g. glypican, syndecan, betaglycan), the polysaccharide hyaluronan and proteins bound to these polysaccharides.
      Nomenclature and definitions
      Glycoconjugates: Various types of compounds consisting of carbohydrates covalently linked with other types of chemical constituent.
      Glycolipids: lipids with a carbohydrate attached by a covalent glycosidic bond. The carbohydrate portion may be a single monosaccharide or a linear or branched chain.
      Glycoproteins: proteins containing oligosaccharide chains (glycans) covalently attached to amino acid side-chains; the carbohydrate portion consists of short chains, often branched.
      Proteoglycans: proteins that are heavily glycosylated; the protein portion of the molecule represents only a small portion of the total molecular weight; the carbohydrate portion consists of long unbranched repeating disaccharide units (glycosaminoglycans, a.k.a. mucopolysaccharides). The three major classes of proteoglycans, characterized by their side chains, are the heparan sulfate proteoglycans, chondroitin sulfate proteoglycans, and keratan sulfate proteoglycans.
      Polysaccharides: polymeric carbohydrate molecules composed of relatively long chains of monosaccharide units bound together by glycosidic linkages.
      Lipopolysaccharides: large molecules consisting of a lipid and a polysaccharide composed of O-antigen, outer core, and inner core joined by a covalent bond; they are typically found in the outer membrane of Gram-negative BACTERIA. They are also known as lipoglycans and endotoxins.
      Peptidoglycans: polymers consisting of amino acids and specific sugars — alternating residues of β-(1,4) linked N-acetylglucosamine (NAG) and N-acetylmuramic acid (NAM) — that form a mesh-like layer outside the plasma membrane of most BACTERIA; they are also known as mureins.


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      Linked Article

      • Dual roles of heparanase in human carotid plaque calcification
        AtherosclerosisVol. 283
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          Calcification is a hallmark of advanced atherosclerosis and an active process akin to bone remodeling. Heparanase (HPSE) is an endo-β-glucuronidase, which cleaves glycosaminoglycan chains of heparan sulfate proteoglycans. The role of HPSE is controversial in osteogenesis and bone remodeling while it is unexplored in vascular calcification. Previously, we reported upregulation of HPSE in human carotid endarterectomies from symptomatic patients and showed correlation of HPSE expression with markers of inflammation and increased thrombogenicity.
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