出版社:American Society for Biochemistry and Molecular Biology
摘要:Phosphatidylcholine transfer protein (PC-TP) is a cytosolicphospholipid binding protein and a member of the steroidogenicacute regulatory-related transfer domain superfamily. Its tissuedistribution includes liver and macrophages. PC-TP regulateshepatic lipid metabolism, and its absence in cholesterol-loadedmacrophages is associated with reduced ATP binding cassettetransporter A1-mediated lipid efflux and increased susceptibilityto apoptosis induced by unesterified cholesterol. To explorea role for PC-TP in atherosclerosis, we prepared PC-TP-deficient/apolipoproteinE-deficient (Pctp–/–/Apoe–/–) mice andlittermate Apoe–/– controls. At 16 weeks, atherosclerosiswas increased in chow-fed male, but not female, Pctp–/–/Apoe–/–mice. This effect was associated with increases in plasma lipidconcentrations. By contrast, no differences in atherosclerosiswere observed between male or female Pctp–/–/Apoe–/–mice and Apoe–/– controls fed a Western-type dietfor 16 weeks. At 24 weeks, atherosclerosis in chow-fed malePctp–/–/Apoe–/– mice tended to be reducedin proportion to plasma cholesterol. The attenuation of atherosclerosisin female Pctp–/–/Apoe–/– mice fed chowor the Western-type diet for 24 weeks was not attributable tochanges in plasma cholesterol or triglyceride concentrations.These findings suggest that PC-TP modulates the developmentof atherosclerosis, in part by regulating plasma lipid concentrations.Supplementary key words phosphatidylcholine transfer protein • steroidogenic acute regulatory-related transfer domain • cholesterol • triglycerides • aorta • macrophage
Abbreviations: apoE, apolipoprotein E; PC-TP, phosphatidylcholine transfer protein; START, steroidogenic acute regulatory-related transfer