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Papers In Press, published online ahead of print March 1, 2007
J. Lipid Res., doi:10.1194/jlr.M600301-JLR200

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Journal of Lipid Research, Vol. 48, 646-655, March 2007
Copyright © 2007 by American Society for Biochemistry and Molecular Biology

Effects of lipoprotein lipase and statins on cholesterol uptake into heart and skeletal muscle

Masayoshi Yokoyama^*, Toru Seo, Taesik Park^*, Hiroaki Yagyu^*, Yunying Hu^*, Ni Huiping Son^*, Ayanna S. Augustus^*, Reeba K. Vikramadithyan^*, Rajasekhar Ramakrishnan, Leslie K. Pulawa, Robert H. Eckel and Ira J. Goldberg^1,*

^* Department of Medicine, Columbia University, New York, NY 10032
Department of Pediatrics and Institute of Human Nutrition, Columbia University, New York, NY 10032
Department of Medicine and Center for Human Nutrition, University of Colorado at Denver and Health Sciences Center, Aurora, CO 80045

The online version of this article (available at http://www.jlr.org) contains additional two figures.

Published, JLR Papers in Press, December 22, 2006.

¹ To whom correspondence should be addressed. e-mail: ijg3{at}columbia.edu

Regulation of cholesterol metabolism in cultured cells and in the 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 primarily hydrolyzes plasma triglyceride into fatty acids. In this study, LDL uptake and tissue cholesterol levels in heart and skeletal muscle of wild-type and transgenic mice with alterations in LPL expression were assessed. Overexpression of a myocyte-anchored form of LPL in heart muscle led to increased uptake of LDL and greater heart cholesterol levels. Loss of LDL receptors did not alter LDL uptake into heart or skeletal muscle. To induce LDL receptors, mice were treated with simvastatin. Statin treatment increased LDL receptor expression and LDL uptake by liver and skeletal muscle but not heart muscle. Plasma creatinine phosphokinase as well as muscle mitochondria, cholesterol, and lipid droplet levels were increased in statin-treated mice overexpressing LPL in skeletal muscle. Thus, pathways affecting cholesterol balance 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

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