Effects of lipoprotein lipase and statins on cholesterol uptake into heart and skeletal muscle.
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.
Yokoyama
Masayoshi
M
Department of Medicine, Columbia University, New York, NY 10032, USA.
Seo
Toru
T
Park
Taesik
T
Yagyu
Hiroaki
H
Hu
Yunying
Y
Son
Ni Huiping
NH
Augustus
Ayanna S
AS
Vikramadithyan
Reeba K
RK
Ramakrishnan
Rajasekhar
R
Pulawa
Leslie K
LK
Eckel
Robert H
RH
Goldberg
Ira J
IJ
D000818:Animals; D015152:Blotting, Northern; D002784:Cholesterol / Q000378:metabolism* / Q000493:pharmacokinetics; D008078:Cholesterol, LDL / Q000378:metabolism / Q000493:pharmacokinetics; D003402:Creatine Kinase / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006321:Heart / Q000187:drug effects; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D050356:Lipid Metabolism / Q000187:drug effects; D008071:Lipoprotein Lipase / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D046529:Microscopy, Electron, Transmission; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D009206:Myocardium / Q000378:metabolism* / Q000648:ultrastructure; D018110:Receptors, Lipoprotein / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019821:Simvastatin / Q000494:pharmacology
D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D018110:Receptors, Lipoprotein; D002784:Cholesterol; D019821:Simvastatin; D003402:Creatine Kinase; D008071:Lipoprotein Lipase