title: Biochemical and cytotoxic characteristics of an in vivo circulating oxidized low density lipoprotein (LDL-).
abstract: Using ion exchange high pressure liquid chromatography, total plasma low density lipoprotein (LDL) from 30 hypercholesterolemic and 10 normocholesterolemic cynomolgus monkeys was subfractionated into unmodified LDL (n-LDL) and more negatively charged LDL (LDL-). In hypercholesterolemic monkeys, the absolute LDL-cholesterol level was 16.54 +/- 2.82 mg/dl (mean +/- SE) whereas in normocholesterolemic monkeys it was 2.39 +/- 0.12 mg/dl (P < 0.0001); the percentage of LDL- was 5.2 +/- 0.71% and 4.9 +/- 0.19% of the total LDL for hypercholesterolemic versus normocholesterolemic monkeys, respectively. LDL- averaged 5% and n-LDL 95% of the total plasma LDL cholesterol. To confirm and further elucidate the oxidative nature of LDL-, cholesterol and cholesterol oxide contents of LDL- and n-LDL were determined by capillary gas chromatography; 53.98 +/- 2.24% (mean +/- SE) of the LDL- cholesterol was oxidized whereas in n-LDL only 10.70 +/- 1.06% of the cholesterol was oxidized (P < 0.00001). The spectrum of oxysterols identified, which was similar for LDL- and n-LDL, suggested a free radical-mediated process for cholesterol oxidation. The principal oxysterols identified were: cholest-5-ene-3 beta, 7 alpha-diol, cholesta-3,5-diene-7-one, cholest-5-ene-3 beta, 7 beta-diol, 5,6 beta-epoxy-5 beta-cholestan-3 beta-ol, 5,6 alpha-epoxy-5 alpha-cholestan-3 beta-ol, 5 alpha-cholestan-3 beta,5,6 beta-triol, 3 beta-hydroxycholest-5-ene-7-one, and cholest-5-ene-3 beta,25-diol. To model one of the steps in the possible mechanism of atherogenesis, the cytotoxicity of LDL- was demonstrated to be greater against subconfluent than confluent aortic endothelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Atherosclerosis Research Institute, University of Southern California School of Medicine, Los Angeles 90033.
authors.forename: H N
authors.initials: HN
authors.lastname: Hodis
authors.forename: D M
authors.initials: DM
authors.lastname: Kramsch
authors.forename: P
authors.initials: P
authors.lastname: Avogaro
authors.forename: G
authors.initials: G
authors.lastname: Bittolo-Bon
authors.forename: G
authors.initials: G
authors.lastname: Cazzolato
authors.forename: J
authors.initials: J
authors.lastname: Hwang
authors.forename: H
authors.initials: H
authors.lastname: Peterson
authors.forename: A
authors.initials: A
authors.lastname: Sevanian
mesh_terms: D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology; D002478:Cells, Cultured; D008078:Cholesterol, LDL / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood* / Q000633:toxicity; D008252:Macaca fascicularis; D010084:Oxidation-Reduction; D011817:Rabbits
chemical_list: D008078:Cholesterol, LDL; D008077:Lipoproteins, LDL