Submitted on July 12, 2006
Revised on November 8, 2006
Accepted on December 21, 2006
Cholesterol uptake into heart and skeletal muscle of lipoprotein lipase transgenic mice: Evidence that statin therapy increases muscle lipid uptake
Masayoshi Yokayama, Toru Seo, Taisik Park, Hiroaki Yagyu, Yunying Hu, Ni Huiping Son, Ayanna S. Augustus, Reeba K. Vikramadythian, Rajasekhar Ramakrishnan, Leslie K. Pulawa, Robert H. Eckel, and Ira J. Goldberg
Medicine, Columbia University, NYC, NY 10032
Corresponding Author: ijg3{at}columbia.edu
Regulation of cholesterol metabolism in cultured cells and in the liver is dependent on actions of the LDL receptor. However, non-hepatic tissues have multiple pathways of cholesterol uptake. One possible pathway is mediated by lipoprotein lipase (LpL), an enzyme that primarily hydrolyzes plasma triglyceride into fatty acids (FAs). LDL uptake and tissue cholesterol levels in hearts and skeletal muscles of wild type and transgenic mice with alterations in LpL expression was 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, but not heart muscle. Plasma creatinine phosphokinase, and 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.
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