Soluble vascular adhesion protein-1 accumulates in proliferative diabetic retinopathy

Miyuki Murata, Kousuke Noda, Junichi Fukuhara, Atsuhiro Kanda, Satoru Kase, Wataru Saito, Yoko Ozawa, Satsuki Mochizuki, Shioko Kimura, Yukihiko Mashima, Yasunori Okada, Susumu Ishida

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)


PURPOSE. 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.

Original languageEnglish
Pages (from-to)4055-4062
Number of pages8
JournalInvestigative Ophthalmology and Visual Science
Issue number7
Publication statusPublished - 2012 Jun
Externally publishedYes

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience


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