title: Preferential binding of oxidized LDL to rat glomeruli in vivo and cultured mesangial cells in vitro.
abstract: Hyperlipidemia may contribute to the pathogenesis of glomerular sclerosis. We therefore compared binding and uptake of native LDL and oxidized LDL (Ox-LDL) to cultured mesangial cells (MC) and the resulting effects on prostaglandin generation and cell proliferation. Ox-LDL, prepared from native LDL by incubation with copper, was bound to MC in a concentration dependent manner with a four- to fivefold increase in binding over LDL. In competition binding experiments Ox-LDL competed to 90% with LDL for binding sites, but LDL only displaced Ox-LDL to 15%. Furthermore polyinosinic acid, which blocks binding of Ox-LDL to macrophages, inhibited binding of Ox-LDL but not that of LDL to MC. Mesangial cells also preferentially took up Ox-LDL over LDL, and Ox-LDL resulted in higher [14C] oleate incorporation into cholesteryl esters than LDL, findings consistent with different handling of Ox-LDL and LDL by MC. LDL slightly stimulated mesangial cell proliferation at low concentration (10 to 50 micrograms/ml of LDL) returning to control levels at 100 and 250 micrograms/ml. In contrast Ox-LDL inhibited cell proliferation in a concentration-dependent manner, starting at concentrations as low as 10 to 25 micrograms/ml of Ox-LDL. Direct observations of mesangial cells by phase contrast microscopy confirmed the cytotoxic effects of Ox-LDL. Addition of Ox-LDL to mesangial cells resulted in a concentration-dependent increase in PGE2 synthesis within one hour, while at this time point LDL had no significant effect.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Medicine, Albert Einstein College of Medicine, Bronx, New York.
authors.forename: G
authors.initials: G
authors.lastname: Coritsidis
authors.forename: V
authors.initials: V
authors.lastname: Rifici
authors.forename: S
authors.initials: S
authors.lastname: Gupta
authors.forename: J
authors.initials: J
authors.lastname: Rie
authors.forename: Z H
authors.initials: ZH
authors.lastname: Shan
authors.forename: J
authors.initials: J
authors.lastname: Neugarten
authors.forename: D
authors.initials: D
authors.lastname: Schlondorff
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D015232:Dinoprostone / Q000378:metabolism; D004587:Electrophoresis, Agar Gel; D005920:Glomerular Mesangium / Q000166:cytology / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism* / Q000493:pharmacokinetics; D008297:Male; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D008077:Lipoproteins, LDL; D015232:Dinoprostone