Glucose degradation product methylglyoxal enhances the production of vascular endothelial growth factor in peritoneal cells: role in the functional and morphological alterations of peritoneal membranes in peritoneal dialysis

FEBS Lett. 1999 Dec 17;463(3):260-4. doi: 10.1016/s0014-5793(99)01642-7.

Abstract

Peritoneal membrane permeability deteriorates in peritoneal dialysis (PD) patients. We test whether glucose degradation products (GDPs) in PD fluids, glyoxal, methylglyoxal and 3-deoxyglucosone, stimulate the production of vascular endothelial growth factor (VEGF), a factor known to enhance vascular permeability and angiogenesis. VEGF increased in cultured rat mesothelial and human endothelial cells exposed to methylglyoxal, but not to glyoxal or 3-deoxyglucosone. VEGF also increased in peritoneal tissue of rats given intraperitoneally methylglyoxal. VEGF and carboxymethyllysine (CML) (formed from GDPs) co-localized immunohistochemically in mesothelial layer and vascular walls of the peritoneal membrane of patients given chronic PD. By contrast, in the peritoneum of non-uremic subjects, VEGF was identified only in vascular walls, in the absence of CML. VEGF production induced by GDPs may play a role in the progressive deterioration of the peritoneal membrane.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Membrane Permeability
  • Cells, Cultured
  • Endothelial Growth Factors / analysis
  • Endothelial Growth Factors / biosynthesis*
  • Epithelial Cells / metabolism
  • Glucose / metabolism*
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Peritoneal Dialysis
  • Peritoneum / blood supply
  • Peritoneum / metabolism*
  • Pyruvaldehyde / analysis
  • Pyruvaldehyde / metabolism*
  • Rats

Substances

  • Endothelial Growth Factors
  • Pyruvaldehyde
  • Glucose