title: Advanced glycation end products increase permeability of brain microvascular endothelial cells through reactive oxygen species-induced vascular endothelial growth factor expression.
abstract: BACKGROUND
  Advanced glycation end products (AGEs) have been implicated as important factors in the pathogenesis of diabetic vascular complication. The aim of this study is to reveal the effect of AGEs on permeability of brain microvascular endothelial cells (BMECs) in order to assess its role in diabetic vascular complications.
  
  
  METHODS
  Permeability was determined by the flux of fluorescein isothiocyanate (FITC)-labeled dextran (4-kDa molecular weight) through endothelial cell monolayers on a transwell system and was compared between bovine BMECs (BBMECs) and bovine aortic endothelial cells (BAECs). The effect of AGEs on permeability was investigated in terms of the role of vascular endothelial growth factor (VEGF) and reactive oxygen species (ROS).
  
  
  RESULTS
  Permeability and VEGF expression were significantly increased by the addition of 100 μg/mL of glycer-AGEs in BBMECs. They also tended to be increased in BAECs, but not enough to make a significant difference. Simultaneous treatment with an anti-VEGF antibody suppressed the AGE-enhanced permeability. Furthermore, simultaneous treatment with a free radical scavenger, edaravone, also suppressed the AGE-enhanced permeability and the increase in VEGF mRNA levels and AGE-induced intracellular ROS overproduction.
  
  
  CONCLUSIONS
  These results suggest that BMECs are more susceptible than aortic endothelial cells to AGE-enhanced permeability and that AGE-enhanced permeability is dependent on VEGF expression induced by ROS over production.
authors.affiliation: Department of Neurosurgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Niiya
authors.forename: Takeo
authors.initials: T
authors.lastname: Abumiya
authors.forename: Sho-ichi
authors.initials: S
authors.lastname: Yamagishi
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Takino
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Takeuchi
mesh_terms: D000818:Animals; D001921:Brain / Q000098:blood supply* / Q000378:metabolism*; D002417:Cattle; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000502:physiology; D002561:Cerebrovascular Disorders / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000378:metabolism* / Q000503:physiopathology; D042783:Endothelial Cells / Q000378:metabolism*; D017127:Glycation End Products, Advanced / Q000378:metabolism* / Q000633:toxicity; D008833:Microcirculation / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
chemical_list: D017127:Glycation End Products, Advanced; D042461:Vascular Endothelial Growth Factor A