title: Upregulated Expression of Heparanase in the Vitreous of Patients With Proliferative Diabetic Retinopathy Originates From Activated Endothelial Cells and Leukocytes.
abstract: OBJECTIVE
  To determine and interrelate the levels of heparanase, syndecan-1, and VEGF in proliferative diabetic retinopathy (PDR), and to study the production of heparanase by human retinal microvascular endothelial cells (HRMEC) and its effect on HRMEC barrier function.
  
  
  METHODS
  Vitreous samples from 33 PDR and 27 nondiabetic patients, epiretinal membranes from 16 patients with PDR and HRMEC were studied by enzyme-linked immunosorbent assay, immunohistochemistry, and Western blot analysis. The effect of heparanase on HRMEC barrier function was evaluated by transendothelial electrical resistance.
  
  
  RESULTS
  We showed a significant increase in the expression of heparanase, syndecan-1, and VEGF in vitreous samples from PDR patients compared with nondiabetic controls (P < 0.0001 for all comparisons). Significant positive correlations were found between the levels of heparanase and the levels of syndecan-1 (r = 0.75, P < 0.0001) and VEGF (r = 0.91, P < 0.0001) and between the levels of syndecan-1 and the levels of VEGF (r = 0.78, P < 0.0001). In epiretinal membranes, heparanase was expressed in vascular endothelial cells and CD45-expressing leukocytes. High-glucose, tumor necrosis factor alpha (TNF-α), and the combination of TNF-α and interleukin (IL)-1β, but not cobalt chloride induced upregulation of heparanase in HRMEC. Heparanase-reduced transendothelial electrical resistance of HRMEC.
  
  
  CONCLUSIONS
  Our findings suggest a link between heparanase, syndecan-1, and VEGF in the progression of PDR and that heparanase is a potential target for therapy of diabetic retinopathy.
authors.affiliation: Department of Ophthalmology College of Medicine, King Saud University, Riyadh, Saudi Arabia 2Dr. Nasser Al-Rashid Research Chair in Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: Abu El-Asrar
authors.affiliation: Department of Ophthalmology College of Medicine, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Kaiser
authors.initials: K
authors.lastname: Alam
authors.affiliation: Department of Ophthalmology College of Medicine, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Mohd Imtiaz
authors.initials: MI
authors.lastname: Nawaz
authors.affiliation: Department of Ophthalmology College of Medicine, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Ghulam
authors.initials: G
authors.lastname: Mohammad
authors.affiliation: Laboratory of Histochemistry and Cytochemistry, University of Leuven, KU Leuven, Leuven, Belgium.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Van den Eynde
authors.affiliation: Department of Ophthalmology College of Medicine, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Mohammad Mairaj
authors.initials: MM
authors.lastname: Siddiquei
authors.affiliation: Department of Ophthalmology College of Medicine, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Mousa
authors.affiliation: Laboratory of Histochemistry and Cytochemistry, University of Leuven, KU Leuven, Leuven, Belgium.
authors.forename: Gert
authors.initials: G
authors.lastname: De Hertogh
authors.affiliation: Laboratory of Histochemistry and Cytochemistry, University of Leuven, KU Leuven, Leuven, Belgium.
authors.forename: Karel
authors.initials: K
authors.lastname: Geboes
authors.affiliation: Rega Institute for Medical Research, Department of Microbiology and Immunology, University of Leuven, KU Leuven, Leuven, Belgium.
authors.forename: Ghislain
authors.initials: G
authors.lastname: Opdenakker
mesh_terms: D015153:Blotting, Western; D002478:Cells, Cultured; D003930:Diabetic Retinopathy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005786:Gene Expression Regulation; D005966:Glucuronidase / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D007962:Leukocytes / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012313:RNA / Q000235:genetics*; D012160:Retina / Q000378:metabolism / Q000473:pathology*; D015854:Up-Regulation; D000099175:Heparanase
chemical_list: D005966:Glucuronidase; D012313:RNA; D000099175:Heparanase