The angiogenic biomarker endocan is upregulated in proliferative diabetic retinopathy and correlates with vascular endothelial growth factor

Curr Eye Res. 2015 Mar;40(3):321-31. doi: 10.3109/02713683.2014.921312. Epub 2014 May 28.

Abstract

Purpose/aim: 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.

Materials and 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.

Keywords: Angiogenesis; endocan; endothelial cell-specific molecule-1; proliferative diabetic retinopathy; vascular endothelial growth factor; vascular endothelial-cadherin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Angiogenic Proteins / metabolism*
  • Antigens, CD / metabolism
  • Biomarkers / metabolism*
  • Cadherins / metabolism
  • Diabetic Retinopathy / metabolism*
  • Diabetic Retinopathy / pathology
  • Diabetic Retinopathy / surgery
  • Endoglin
  • Enzyme-Linked Immunosorbent Assay
  • Epiretinal Membrane / metabolism
  • Epiretinal Membrane / surgery
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Neoplasm Proteins / metabolism*
  • Proteoglycans / metabolism*
  • Receptors, Cell Surface / metabolism
  • Retinal Neovascularization / metabolism*
  • Retinal Neovascularization / pathology
  • Retinal Neovascularization / surgery
  • Up-Regulation
  • Vascular Endothelial Growth Factor A / metabolism*
  • Vitrectomy
  • Vitreous Body / metabolism*

Substances

  • Angiogenic Proteins
  • Antigens, CD
  • Biomarkers
  • Cadherins
  • ENG protein, human
  • ESM1 protein, human
  • Endoglin
  • Neoplasm Proteins
  • Proteoglycans
  • Receptors, Cell Surface
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • cadherin 5