title: The angiogenic biomarker endocan is upregulated in proliferative diabetic retinopathy and correlates with vascular endothelial growth factor.
abstract: OBJECTIVE
  Endocan is a proteoglycan specifically secreted by endothelial cells, is a marker of angiogenesis and endothelial cell activation in response to proangiogenic signals. The aim of this study was to measure the levels of endocan in the vitreous fluid from patients with proliferative diabetic retinopathy (PDR) and to correlate its levels with clinical disease activity and the levels of the angiogenic biomarkers vascular endothelial growth factor (VEGF), soluble vascular endothelial-cadherin (sVE-cadherin) and soluble endoglin (sEng). In addition, we investigated the expression of endocan and correlated it with the level of vascularization in PDR epiretinal membranes.
  
  
  METHODS
  Vitreous samples from 44 PDR and 29 non-diabetic patients were studied by enzyme-linked immunosorbent assay. Epiretinal membranes from 14 patients with PDR were studied by immunohistochemistry.
  
  
  RESULTS
  Endocan, VEGF, sVE-cadherin and sEng levels were significantly higher in PDR patients than in non-diabetic patients (p < 0.001; p = 0.002; p < 0.001; p = 0.001, respectively). Endocan levels were significantly higher in patients with active PDR than in patients with inactive PDR and non-diabetic patients (p < 0.001). There were significant positive correlations between endocan levels and the levels of VEGF (r = 0.574, p < 0.001) and sVE-cadherin (r = 0.498, p < 0.001). In epiretinal membranes, vascular endothelial cells and myofibroblasts expressed endocan. There was a significant positive correlation between the number of blood vessels expressing CD34 and the number of blood vessels expressing endocan (r = 0.933, p < 0.001).
  
  
  CONCLUSIONS
  Our findings suggest that upregulation of endocan expression in PDR could be a reflection of endothelial cell activation associated with angiogenesis.
authors.affiliation: Department of Ophthalmology, College of Medicine, King Saud University , Riyadh , Saudi Arabia and.
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: Abu El-Asrar
authors.forename: Mohd Imtiaz
authors.initials: MI
authors.lastname: Nawaz
authors.forename: Gert
authors.initials: G
authors.lastname: De Hertogh
authors.forename: Abdullah S
authors.initials: AS
authors.lastname: Al-Kharashi
authors.forename: Kathleen
authors.initials: K
authors.lastname: Van den Eynde
authors.forename: Ghulam
authors.initials: G
authors.lastname: Mohammad
authors.forename: Karel
authors.initials: K
authors.lastname: Geboes
mesh_terms: D000368:Aged; D042501:Angiogenic Proteins / Q000378:metabolism*; D015703:Antigens, CD / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism; D003930:Diabetic Retinopathy / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D000071063:Endoglin; D004797:Enzyme-Linked Immunosorbent Assay; D019773:Epiretinal Membrane / Q000378:metabolism / Q000601:surgery; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D011509:Proteoglycans / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism; D015861:Retinal Neovascularization / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D014821:Vitrectomy; D014822:Vitreous Body / Q000378:metabolism*; D000099152:Cadherin 5
chemical_list: D042501:Angiogenic Proteins; D015703:Antigens, CD; D015415:Biomarkers; D015820:Cadherins; D000071063:Endoglin; D009363:Neoplasm Proteins; D011509:Proteoglycans; D011956:Receptors, Cell Surface; D042461:Vascular Endothelial Growth Factor A; D000099152:Cadherin 5; C064206:ENG protein, human; C101134:ESM1 protein, human; C467484:VEGFA protein, human
keywords: Angiogenesis; endocan; endothelial cell-specific molecule-1; proliferative diabetic retinopathy; vascular endothelial growth factor; vascular endothelial-cadherin