title: Soluble vascular adhesion protein-1 accumulates in proliferative diabetic retinopathy.
abstract: OBJECTIVE
  Vascular adhesion protein (VAP)-1, a multifunctional molecule with adhesive and enzymatic properties, is expressed at the surface of vascular endothelial cells of mammals. It also exists as a soluble form (sVAP-1), which is implicated in oxidative stress via its enzymatic activity. This study explores a link between increased level of sVAP-1 and oxidative stress in proliferative diabetic retinopathy (PDR) with a focus on mechanistic components to form sVAP-1 by shedding from retinal endothelial cells.
  
  
  METHODS
  Protein levels of sVAP-1 and N epsilon-(hexanoyl)lysine (HEL), an oxidative stress marker, in the vitreous samples from patients with PDR or non-PDR were measured by ELISA. The mechanism of VAP-1 shedding under diabetic condition, exposure to high glucose and/or inflammatory cytokines, was explored using cultured retinal capillary endothelial cells.
  
  
  RESULTS
  Protein level of sVAP-1 was increased and correlated with HEL in the vitreous fluid of patients with PDR. Retinal capillary endothelial cells released sVAP-1 when stimulated with high glucose or inflammatory cytokines, such as TNF-α and IL-1β in vitro. Furthermore, matrix metalloproteinase-2 and -9, type IV collagenases, were the key molecules to mediate the protein cleavage of VAP-1 from retinal capillary endothelial cells.
  
  
  CONCLUSIONS
  Our data for the first time provide evidence on the link between sVAP-1 and type IV collagenases in the pathogenesis of PDR.
authors.affiliation: Laboratory of Ocular Cell Biology & Visual Science, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Murata
authors.forename: Kousuke
authors.initials: K
authors.lastname: Noda
authors.forename: Junichi
authors.initials: J
authors.lastname: Fukuhara
authors.forename: Atsuhiro
authors.initials: A
authors.lastname: Kanda
authors.forename: Satoru
authors.initials: S
authors.lastname: Kase
authors.forename: Wataru
authors.initials: W
authors.lastname: Saito
authors.forename: Yoko
authors.initials: Y
authors.lastname: Ozawa
authors.forename: Satsuki
authors.initials: S
authors.lastname: Mochizuki
authors.forename: Shioko
authors.initials: S
authors.lastname: Kimura
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Mashima
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Okada
authors.forename: Susumu
authors.initials: S
authors.lastname: Ishida
mesh_terms: D006631:Amine Oxidase (Copper-Containing) / Q000096:biosynthesis / Q000235:genetics*; D015153:Blotting, Western; D002196:Capillaries / Q000378:metabolism / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000235:genetics*; D002478:Cells, Cultured; D004247:DNA / Q000235:genetics*; D003930:Diabetic Retinopathy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D047468:Immunoprecipitation; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D018384:Oxidative Stress; D012171:Retinal Vessels / Q000378:metabolism* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012795:Sialoglycoproteins; D014821:Vitrectomy; D018630:Vitreoretinopathy, Proliferative / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D014822:Vitreous Body / Q000378:metabolism* / Q000601:surgery
chemical_list: D015815:Cell Adhesion Molecules; D012795:Sialoglycoproteins; D004247:DNA; C076668:AOC3 protein, human; D006631:Amine Oxidase (Copper-Containing)