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

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Abstract

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
Volume53
Issue number7
DOIs
Publication statusPublished - 2012 Jun

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ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience
  • Medicine(all)

Cite this

Murata, M., Noda, K., Fukuhara, J., Kanda, A., Kase, S., Saito, W., Ozawa, Y., Mochizuki, S., Kimura, S., Mashima, Y., Okada, Y., & Ishida, S. (2012). Soluble vascular adhesion protein-1 accumulates in proliferative diabetic retinopathy. Investigative Ophthalmology and Visual Science, 53(7), 4055-4062. https://doi.org/10.1167/iovs.12-9857