Evidence for inhibition of low density lipoprotein oxidation and cholesterol accumulation by apolipoprotein H (beta2-glycoprotein I).
Low density lipoprotein (LDL) oxidation and lipid accumulation are thought to enhance the progression of atherosclerosis. Apolipoprotein H (apoH) has been implicated in the development of human atherosclerosis. However, the roles of apoH in the oxidative modification of LDL and cellular accumulation of lipid constituents remained uncharacterized. In this study, the level of plasma apoH was found to be significantly associated with the oxidative susceptibility of LDL in human subjects. Plasma levels of apoH were positively correlated with the lag time but negatively correlated with LDL oxidation rate in conjugated diene formation. By using a J774 A.1 macrophage culture system, we found that apoH could not only inhibit the formation of conjugated diene and thiobarbituric acid-reactive substances, but also reduce the electrophoretic mobility of oxidized LDL. Furthermore, apoH decreased cellular accumulation of cholesterol via a reduction in cholesterol influx and an increase in cholesterol efflux. This is the first demonstration that apoH appears to have "antioxidant"-like effects on LDL oxidation. The results also suggest that apoH can inhibit the translocation of cholesterol from extracellular pools to macrophages, suggesting that apoH may play an important role in the prevention of atherosclerosis.
Lin
K Y
KY
Institute of Biochemistry, National Yang-Ming University, Taipei, Taiwan, ROC.
Pan
J P
JP
Yang
D L
DL
Huang
K T
KT
Chang
M S
MS
Ding
P Y
PY
Chiang
A N
AN
D001161:Arteriosclerosis / Q000097:blood; D002478:Cells, Cultured; D002784:Cholesterol / Q000096:biosynthesis*; D017077:Culture Media, Conditioned / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D006023:Glycoproteins / Q000097:blood / Q000494:pharmacology*; D006787:Hospitals, Veterans; D006801:Humans; D008077:Lipoproteins, LDL / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000097:blood / Q000494:pharmacology*; D010084:Oxidation-Reduction; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014728:Veterans; D053482:beta 2-Glycoprotein I
D017077:Culture Media, Conditioned; D006023:Glycoproteins; D008077:Lipoproteins, LDL; D008562:Membrane Glycoproteins; D017392:Thiobarbituric Acid Reactive Substances; D053482:beta 2-Glycoprotein I; D002784:Cholesterol