Lipoprotein-X reduces LDL atherogenicity in primary biliary cirrhosis by preventing LDL oxidation
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...
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| Language: | English |
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Elsevier
2004-11-01
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| Series: | Journal of Lipid Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520341420 |
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| author | Po-Yuan Chang Shao-Chun Lu Ta-Chen Su San-Fang Chou Wen-Huei Huang Joel D. Morrisett Chu-Huang Chen Chiau-Suong Liau Yuan-Teh Lee |
| author_facet | Po-Yuan Chang Shao-Chun Lu Ta-Chen Su San-Fang Chou Wen-Huei Huang Joel D. Morrisett Chu-Huang Chen Chiau-Suong Liau Yuan-Teh Lee |
| author_sort | Po-Yuan Chang |
| collection | DOAJ |
| description | 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. |
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| institution | Directory Open Access Journal |
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| language | English |
| last_indexed | 2024-12-20T01:22:21Z |
| publishDate | 2004-11-01 |
| publisher | Elsevier |
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| series | Journal of Lipid Research |
| spelling | doaj.art-636f45e08c7d42d088ef311d86b713c42022-12-21T19:58:22ZengElsevierJournal of Lipid Research0022-22752004-11-01451121162122Lipoprotein-X reduces LDL atherogenicity in primary biliary cirrhosis by preventing LDL oxidationPo-Yuan Chang0Shao-Chun Lu1Ta-Chen Su2San-Fang Chou3Wen-Huei Huang4Joel D. Morrisett5Chu-Huang Chen6Chiau-Suong Liau7Yuan-Teh Lee8Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Department of Biochemistry and Molecular Biology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Department of Medicine, Baylor College of Medicine, Houston, TXDepartment of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Department of Biochemistry and Molecular Biology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Department of Medicine, Baylor College of Medicine, Houston, TXDepartment of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Department of Biochemistry and Molecular Biology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Department of Medicine, Baylor College of Medicine, Houston, TXDepartment of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Department of Biochemistry and Molecular Biology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Department of Medicine, Baylor College of Medicine, Houston, TXDepartment of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Department of Biochemistry and Molecular Biology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Department of Medicine, Baylor College of Medicine, Houston, TXDepartment of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Department of Biochemistry and Molecular Biology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Department of Medicine, Baylor College of Medicine, Houston, TXDepartment of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Department of Biochemistry and Molecular Biology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Department of Medicine, Baylor College of Medicine, Houston, TXDepartment of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Department of Biochemistry and Molecular Biology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Department of Medicine, Baylor College of Medicine, Houston, TXDepartment of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Department of Biochemistry and Molecular Biology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Department of Medicine, Baylor College of Medicine, Houston, TXHypercholesterolemic 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.http://www.sciencedirect.com/science/article/pii/S0022227520341420hypercholesterolemialow density lipoprotein oxidationfibroblast growth factor 2endothelium |
| spellingShingle | Po-Yuan Chang Shao-Chun Lu Ta-Chen Su San-Fang Chou Wen-Huei Huang Joel D. Morrisett Chu-Huang Chen Chiau-Suong Liau Yuan-Teh Lee Lipoprotein-X reduces LDL atherogenicity in primary biliary cirrhosis by preventing LDL oxidation Journal of Lipid Research hypercholesterolemia low density lipoprotein oxidation fibroblast growth factor 2 endothelium |
| title | Lipoprotein-X reduces LDL atherogenicity in primary biliary cirrhosis by preventing LDL oxidation |
| title_full | Lipoprotein-X reduces LDL atherogenicity in primary biliary cirrhosis by preventing LDL oxidation |
| title_fullStr | Lipoprotein-X reduces LDL atherogenicity in primary biliary cirrhosis by preventing LDL oxidation |
| title_full_unstemmed | Lipoprotein-X reduces LDL atherogenicity in primary biliary cirrhosis by preventing LDL oxidation |
| title_short | Lipoprotein-X reduces LDL atherogenicity in primary biliary cirrhosis by preventing LDL oxidation |
| title_sort | lipoprotein x reduces ldl atherogenicity in primary biliary cirrhosis by preventing ldl oxidation |
| topic | hypercholesterolemia low density lipoprotein oxidation fibroblast growth factor 2 endothelium |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520341420 |
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