[Lipoprotein lipase-mediated myopathy: implications for lipid metabolism and atherogenesis].
BACKGROUND
Lipoprotein lipase (LPL) is the central enzyme in plasma triglyceride hydrolysis. Various genetically modified mouse lines expressing either native or mutated LPL have been established, and the function of LPL in the metabolism and during lipoprotein transport has been characterized. Some of these animals showed an LPL-mediated myopathy or cardiomyopathy. Comparing the histological changes with metabolic data provides new insights in the function of LPL in metabolism and for atherogenesis.


METHODS
Histological and electron microscopy specimens of muscle and heart from different LPL transgenic mouse lines have been evaluated and compared to metabolic data.


RESULTS
Presence of LPL causes a myopathy and cardiomyopathy primarily by augmenting nonenzymatic selective cholesterol ester uptake. LPL-mediated fatty acid and lipoprotein uptake is not sufficient to harm muscle tissue.


CONCLUSIONS
It is suggested, that LPL derived from endothelial cells and macrophages--besides other atherogenic mechanisms--can mediate cholesterol ester influx into the vessel wall and thereby promote proatherogenic modifications. Although due to its hydrolytic function, LPL is generally considered an antiatherogenic enzyme, endothelial LPL can locally facilitate atherogenesis.
Merkel
Martin
M
Medizinische Klinik I, Universitätsklinikum, Hamburg-Eppendorf. merkel@uke.uni-hamburg.de
Radner
Herbert
H
Greten
Heiner
H
D000818:Animals; D001161:Arteriosclerosis / Q000201:enzymology / Q000209:etiology* / Q000378:metabolism; D003327:Coronary Disease / Q000201:enzymology / Q000209:etiology* / Q000378:metabolism; D004195:Disease Models, Animal; D004452:Echocardiography; D004730:Endothelium, Vascular / Q000201:enzymology / Q000378:metabolism; D005260:Female; D005455:Fluorescent Antibody Technique; D050356:Lipid Metabolism; D008071:Lipoprotein Lipase / Q000235:genetics / Q000378:metabolism*; D008074:Lipoproteins / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D009135:Muscular Diseases / Q000201:enzymology / Q000209:etiology* / Q000378:metabolism; D009206:Myocardium / Q000473:pathology; D012307:Risk Factors
D008074:Lipoproteins; D008071:Lipoprotein Lipase