Intracellular oxidative modification of low density lipoprotein by endothelial cells.
We investigated intracellular oxidative modification of low density lipoprotein (IOM-LDL) by endothelial cells (ECs) and the role of ferritin in this process. IOM-LDL was examined by immunocytochemistry with an anti-oxidized phosphatidylcholine antibody and by lipid peroxidation assay. Incubation of LDL-treated ECs (human umbilical vein endothelial cells, passage 3) with ferritin produced cytoplasmic immunostain with the antibody, especially in large or giant ECs, and the formation of thiobarbituric acid-reactive substance (TBARS) in these cells. These observations suggest that ECs can perform IOM-LDL. Incubation with the iron chelator deferoxamine or pretreatment of LDL-treated ECs with deferoxamine suppressed ferritin-induced IOM-LDL by greater than 60%. Antioxidants dimethylsulphoxide and butylated hydroxytoluene markedly inhibited IOM-LDL, but mannitol did so only mildly. Catalase and superoxide dismutase had little or no effect on IOM-LDL. Apoferritin substituted for ferritin did not induce IOM-LDL. Our data suggest that IOM-LDL is mediated by intracellular hydroxyl radical formation, which is catalyzed mainly by free iron released from ferritin, and that ECs contribute to the development of atherosclerosis via IOM-LDL.
Satoh
Toshimi
T
Department of Pathology, Saga Medical School, 5-1-1 Nabeshima, Saga 849-8501, Japan. satoht2@post.saga-med.ac.jp
Tokunaga
Osamu
O
D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005293:Ferritins / Q000378:metabolism / Q000494:pharmacology; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D015227:Lipid Peroxidation; D008077:Lipoproteins, LDL / Q000378:metabolism*; D014471:Umbilical Veins / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
D008077:Lipoproteins, LDL; D005293:Ferritins