Metabolism of oxidized glycated low-density lipoprotein in cultured bovine aortic endothelial cells.
The serum concentration of glycated low-density lipoprotein (gLDL) is increased in individuals with diabetes mellitus, which may be a contributing factor to the increased incidence of atherosclerosis in this population. Given the importance of oxidized LDL (oLDL) in atherosclerosis and that vascular endothelial cells express receptors for oLDL, oxidized glycated LDL (ogLDL) was prepared in vitro and its binding and degradation by cultured bovine aortic endothelial cells were examined. Glycation of native LDL (nLDL) isolated from normal human subjects was performed by incubation with 20 mM glucose at 37 degrees C for 3 days, and ogLDL was prepared by oxidation of gLDL with 1 microM CuSO4 at 37 degrees C for 12 hours. The electrophoretic mobility and thiobarbituric acid reactive substance (TBARS) value of ogLDL were greater than those of nLDL and gLDL. Both binding and degradation of ogLDL by cultured endothelial cells also were significantly greater than for nLDL and gLDL. Degradation of nLDL by endothelial cells was completely inhibited by ogLDL, whereas degradation of acetylated LDL was not inhibited by nLDL or ogLDL. Thus, the binding and degradation of ogLDL by endothelial cells do not appear to be mediated by the scavenger receptor. Although the exact mechanism is not clear, it appears that vascular endothelial cells may play a protective role against atherosclerosis by removing potential atherogenic lipoproteins.
Kobayashi
K
K
Third Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Watanabe
J
J
Umeda
F
F
Masakado
M
M
Ono
Y
Y
Taniguchi
S
S
Yanase
T
T
Hashimoto
T
T
Sako
Y
Y
Nawata
H
H
D000818:Animals; D001011:Aorta; D001667:Binding, Competitive; D002417:Cattle; D002478:Cells, Cultured; D003300:Copper / Q000494:pharmacology; D019327:Copper Sulfate; D004587:Electrophoresis, Agar Gel; D004730:Endothelium, Vascular / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D010084:Oxidation-Reduction; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D008077:Lipoproteins, LDL; D017392:Thiobarbituric Acid Reactive Substances; C032629:acetyl-LDL; D003300:Copper; D005947:Glucose; D019327:Copper Sulfate