https://scholars.lib.ntu.edu.tw/handle/123456789/533891
標題: | Lipoprotein-X reduces LDL atherogenicity in primary biliary cirrhosis by preventing LDL oxidation | 作者: | PO-YUAN CHANG SHAO-CHUN LU TA-CHEN SU Chou S.-F. Huang W.-H. Morrisett J.D. Chen C.-H. Liau C.-S. Lee Y.-T. |
公開日期: | 2004 | 卷: | 45 | 期: | 11 | 起(迄)頁: | 2116-2122 | 來源出版物: | Journal of Lipid Research | 摘要: | Hypercholesterolemic human LDL contains oxidized subfractions that have atherogenic properties. Paradoxically, atherosclerosis incidence is low in patients with primary biliary cirrhosis (PBC), a disease characterized by marked increases in plasma LDL, including the LDL subfraction lipoprotein-X (Lp-X). To investigate the mechanisms underlying this paradox, we first examined the propensity to oxidation of unfractionated LDL isolated from PBC patients. After prolonged incubation with copper, PBC-LDL failed to increase the oxidation index or electrophoretic mobility noted in control LDL. An admixture of PBC-LDL or Lp-X with control LDL prevented oxidation of the latter in a dose-dependent manner. PBC-LDL was also noncompetitive against copper-oxidized LDL (oxLDL) for binding with a murine monoclonal anti-oxLDL antibody in a competitive ELISA. OxLDL exerts its proapoptotic and antiangiogenic effects in part by inhibiting fibroblast growth factor 2 (FGF2) expression. Preincubation of oxLDL with PBC-LDL, but not control LDL, attenuated the inhibitory effects of oxLDL on FGF2 expression in cultured bovine aortic endothelial cells (ECs). The antioxidant and prosurvival properties of PBC-LDL diminished after the patients underwent orthotopic liver transplantation. These results suggest that Lp-X reduces LDL atherogenicity by preventing LDL oxidation to protect EC integrity in the presence of hypercholesterolemia. They also suggest that altering LDL composition may be as important as reducing LDL concentration in preventing or treating atherosclerosis. Copyright ? 2004 by the American Society for Biochemistry and Molecular Biology, Inc. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-14844319571&doi=10.1194%2fjlr.M400229-JLR200&partnerID=40&md5=c4b6d7b3a02baae1e8a263e5614d46bf https://scholars.lib.ntu.edu.tw/handle/123456789/533891 |
ISSN: | 0022-2275 | DOI: | 10.1194/jlr.M400229-JLR200 | SDG/關鍵字: | bilirubin; copper; fibroblast growth factor 2; lipoprotein X; low density lipoprotein cholesterol; messenger RNA; monoclonal antibody; oxidized low density lipoprotein; fibroblast growth factor 2; ligand; lipoprotein X; low density lipoprotein; oxygen; peptide; adult; angiogenesis; animal cell; antioxidant activity; aorta; apoptosis; article; atherogenesis; atherosclerosis; clinical article; controlled study; cow; enzyme linked immunosorbent assay; female; gel filtration chromatography; gel mobility shift assay; human; hypercholesterolemia; lipid oxidation; liver transplantation; male; nonhuman; primary biliary cirrhosis; priority journal; vascular endothelium; agar gel electrophoresis; animal; biliary cirrhosis; cattle; cell culture; chemistry; cytology; down regulation; gel chromatography; history; metabolism; time; Animals; Aorta; Apoptosis; Cattle; Cells, Cultured; Chromatography, Gel; Down-Regulation; Electrophoresis, Agar Gel; Endothelium, Vascular; Enzyme-Linked Immunosorbent Assay; Fibroblast Growth Factor 2; History, 20th Century; Ligands; Lipoprotein-X; Lipoproteins, LDL; Liver Cirrhosis, Biliary; Oxygen; Peptides; RNA, Messenger; Time Factors |
顯示於: | 醫學系 |
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