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  • 标题:ApoE promotes hepatic selective uptake but not RCT due to increased ABCA1-mediated cholesterol efflux to plasma
  • 本地全文:下载
  • 作者:Wijtske Annema ; Arne Dikkers ; Jan Freark de Boer
  • 期刊名称:JLR Papers In Press
  • 印刷版ISSN:0022-2275
  • 电子版ISSN:1539-7262
  • 出版年度:2012
  • 卷号:53
  • 期号:5
  • 页码:929-940
  • DOI:10.1194/jlr.M020743
  • 语种:English
  • 出版社:American Society for Biochemistry and Molecular Biology
  • 摘要:ApoE plays an important role in lipoprotein metabolism. This study investigated the effects of adenovirus-mediated human apoE overexpression (AdhApoE3) on sterol metabolism and in vivo reverse cholesterol transport (RCT). In wild-type mice, AdhApoE3 resulted in decreased HDL cholesterol levels and a shift toward larger HDL in plasma, whereas hepatic cholesterol content increased ( P P P 3H-cholesterol-loaded mouse macrophage foam cells remained unchanged upon human apoE overexpression. Similar results were obtained using hApoE3 overexpression in human CETP transgenic mice. However, blocking ABCA1-mediated cholesterol efflux from hepatocytes in AdhApoE3-injected mice using probucol increased biliary cholesterol secretion ( P P P i ) SR-BI-mediated selective uptake into the liver and ii ) ABCA1-mediated efflux of RCT-relevant cholesterol from hepatocytes back to the plasma compartment, thereby resulting in unchanged fecal mass sterol excretion and overall in vivo RCT.
  • 关键词:apolipoprotein E ; reverse cholesterol transport ; ATP-binding cassette transporter A1 ; atherosclerosis ; bile ; cholesteryl ester transfer protein ; feces ; high density lipoprotein ; liver ; macrophage ; metabolism ; mice ; probucol
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