文章基本信息

标题：Bile acid and sterol metabolism with combined HMG-CoA reductase and PCSK9 suppression
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作者：Rex A. Parker ; Ricardo Garcia ; Carol S. Ryan 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2013
卷号：54
期号：9
页码：2400-2409
DOI：10.1194/jlr.M038331
语种：English
出版社：American Society for Biochemistry and Molecular Biology
摘要：Proprotein convertase subtilisin-kexin-9 (PCSK9) inhibition markedly augments the LDL lowering action of statins. The combination is being evaluated for long-term effects on atherosclerotic disease outcomes. However, effects of combined treatment on hepatic cholesterol and bile acid metabolism have not yet been reported. To study this, PCSK9-Y119X mutant (knockout) and wild-type mice were treated with or without atorvastatin for 12 weeks. Atorvastatin progressively lowered plasma LDL in each group, but no differences in liver cholesterol, cholesterol ester, or total bile acid concentrations, or in plasma total bile acid levels were seen. In contrast, atorvastatin increased fecal total bile acids (∼2-fold, P P
关键词：proprotein convertase subtilisin-kexin-9 inhibitors ; 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors ; statins ; CYP7A1 ; bile acid transporter ; cholestasis ; low desnsity lipoprotein receptor ; N-ethyl N-nitrosourea mutagenesis