期刊
JOURNAL OF LIPID RESEARCH
卷 52, 期 3, 页码 558-565出版社
ELSEVIER
DOI: 10.1194/jlr.M011080
关键词
Niemann-Pick C1-like 1; cholesterol metabolism; 3-hydroxy-3-methylglutaryl CoA reductase; intestine; low density lipoprotein receptor
资金
- Merck Frosst/Schering Company
- FRSQ
Inhibition of cholesterol synthesis by 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoAR) inhibitors has been associated with an increase in intestinal cholesterol absorption. This study examined how HMG-CoAR inhibition by atorvastatin modulates expression of key genes involved in intestinal cholesterol metabolism. A crossover study was conducted in which 22 hyperlipidemic men received atorvastatin, 40 mg/day, or placebo, each for 12 weeks. Gene expression was assessed by real-time PCR using duodenal biopsy samples obtained at the end of each phase of treatment. Treatment with atorvastatin was associated with a 76% reduction in lathosterol and significant increases in sitosterol (70%). Atorvastatin significantly increased intestinal mRNA levels of HMG-CoAR (59%), LDL receptor (LDLR) (52%), PCSK9 (187%), SREBP-2 (44%), and HNF-4 alpha (13%). Furthermore, atorvastatin significantly increased intestinal mRNA levels of NPC1L1 by 19% and decreased mRNA levels of both ABCG5 and ABCG8 by 14%. Positive correlations were observed between changes in SREBP-2 and HNF-4 alpha expression and concurrent changes in the intestinal mRNA levels of HMG-CoAR, LDLR, and NPC1L1.jlr These results indicate that HMG-CoAR inhibition with atorvastatin stimulates the intestinal expression of NPC1L1, LDLR, and PCSK9; increases cholesterol absorption; and reduces expression of ABCG5/8; these effects are most likely mediated by upregulation of the transcription factors SREBP-2 and HNF-4 alpha.-Tremblay, A. J., B. Lamarche, V. Lemelin, L. Hoos, S. Benjannet, N. G. Seidah, H. R. Davis, Jr., and P. Couture. Atorvastatin increases intestinal expression of NPC1L1 in hyperlipidemic men. J. Lipid Res. 2011. 52: 558-565
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据