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