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标题：Effects of lipoprotein lipase and statins on cholesterol uptake into heart and skeletal muscle
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作者：Yokoyama, Masayoshi ; Seo, Toru ; Park, Taesik 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：2007
卷号：48
期号：3
页码：646-655
DOI：10.1194/jlr.M600301-JLR200
出版社：American Society for Biochemistry and Molecular Biology
摘要：Regulation of cholesterol metabolism in cultured cells and inthe liver is dependent on actions of the LDL receptor. However,nonhepatic tissues have multiple pathways of cholesterol uptake.One possible pathway is mediated by LPL, an enzyme that primarilyhydrolyzes plasma triglyceride into fatty acids. In this study,LDL uptake and tissue cholesterol levels in heart and skeletalmuscle of wild-type and transgenic mice with alterations inLPL expression were assessed. Overexpression of a myocyte-anchoredform of LPL in heart muscle led to increased uptake of LDL andgreater heart cholesterol levels. Loss of LDL receptors didnot alter LDL uptake into heart or skeletal muscle. To induceLDL receptors, mice were treated with simvastatin. Statin treatmentincreased LDL receptor expression and LDL uptake by liver andskeletal muscle but not heart muscle. Plasma creatinine phosphokinaseas well as muscle mitochondria, cholesterol, and lipid dropletlevels were increased in statin-treated mice overexpressingLPL in skeletal muscle. Thus, pathways affecting cholesterolbalance in heart and skeletal muscle differ. Supplementary key words myopathy • hypercholesterolemia • statin Abbreviations: CPK, creatine phosphokinase; HMG-CoA-R, hydroxymethyl glutaryl coenzyme A reductase; Ldlr^–/–, low density lipoprotein receptor knockout; LPL^GPI, glycosylphosphatidyl-inositol-anchored lipoprotein lipase; MCK, muscle creatinine kinase; Srebp2, sterol-regulatory element binding protein 2; TC, tyramine cellobiose; TG, triglyceride