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. MATERIAL AND 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. CONCLUSION: 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.
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. MATERIAL AND 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. CONCLUSION: 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.