title: 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.
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.
authors.affiliation: Molecular and Cellular Nephrology, Institute of Medical Sciences, Department of Internal Medicine, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Inagi
authors.forename: T
authors.initials: T
authors.lastname: Miyata
authors.forename: T
authors.initials: T
authors.lastname: Yamamoto
authors.forename: D
authors.initials: D
authors.lastname: Suzuki
authors.forename: K
authors.initials: K
authors.lastname: Urakami
authors.forename: A
authors.initials: A
authors.lastname: Saito
authors.forename: C
authors.initials: C
authors.lastname: van Ypersele de Strihou
authors.forename: K
authors.initials: K
authors.lastname: Kurokawa
mesh_terms: D000818:Animals; D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D016228:Endothelial Growth Factors / Q000032:analysis / Q000096:biosynthesis*; D004847:Epithelial Cells / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010530:Peritoneal Dialysis; D010537:Peritoneum / Q000098:blood supply / Q000378:metabolism*; D011765:Pyruvaldehyde / Q000032:analysis / Q000378:metabolism*; D051381:Rats
chemical_list: D016228:Endothelial Growth Factors; D011765:Pyruvaldehyde; D005947:Glucose