Endothelial lipase is a major determinant of HDL level.

A new member of the lipase gene family, initially termed endothelial lipase (gene nomenclature, LIPG; protein, EL), is expressed in a variety of different tissues, suggesting a general role in lipid metabolism. To assess the hypothesis that EL plays a physiological role in lipoprotein metabolism in vivo, we have used gene targeting of the native murine locus and transgenic introduction of the human LIPG locus in mice to modulate the level of EL expression. Evaluation of these alleles in a C57Bl/6 background revealed an inverse relationship between HDL cholesterol level and EL expression. Fasting plasma HDL cholesterol was increased by 57% in LIPG(-/-) mice and 25% in LIPG(+/-) mice and was decreased by 19% in LIPG transgenic mice as compared with syngeneic controls. Detailed analysis of lipoprotein particle composition indicated that this increase was due primarily to an increased number of HDL particles. Phospholipase assays indicated that EL is a primary contributor to phospholipase activity in mouse. These data indicate that expression levels of this novel lipase have a significant effect on lipoprotein metabolism.

[1]  D. Rader,et al.  Characterization of the lipolytic activity of endothelial lipase. , 2002, Journal of lipid research.

[2]  P. Libby.  Managing the risk of atherosclerosis: the role of high-density lipoprotein. , 2001, American Journal of Cardiology.

[3]  Jonathan C. Cohen,et al.  An Apolipoprotein Influencing Triglycerides in Humans and Mice Revealed by Comparative Sequencing , 2001, Science.

[4]  R. Lawn,et al.  ABCA1. The gatekeeper for eliminating excess tissue cholesterol. , 2001, Journal of lipid research.

[5]  I. Goldberg,et al.  Caloric and vitamin distribution by LpL 4. Synthesis and processing of lipases 5. Lipoproteins and regulation of the lipolysis reaction 6. Apolipoproteins 7. Non-enzymatic actions of lipoprotein lipase 8. Structure-function analysis of lipoprotein lipase 9.Genetic variation in lipoprotein lipase 10. , 2002 .

[6]  P. Tsao,et al.  Regulated expression of endothelial cell-derived lipase. , 2000, Biochemical and biophysical research communications.

[7]  A. Tall,et al.  Phospholipid transfer protein gene knock-out mice have low high density lipoprotein levels, due to hypercatabolism, and accumulate apoA-IV-rich lamellar lipoproteins. , 2000, Journal of lipid research.

[8]  S. Perrey,et al.  Overexpressed lipoprotein lipase protects against atherosclerosis in apolipoprotein E knockout mice. , 1999, Journal of lipid research.

[9]  M. Linton,et al.  Macrophage lipoprotein lipase promotes foam cell formation and atherosclerosis in vivo. , 1999, The Journal of clinical investigation.

[10]  Sungshin Y. Choi,et al.  Cloning of a Unique Lipase from Endothelial Cells Extends the Lipase Gene Family* , 1999, The Journal of Biological Chemistry.

[11]  D. Rader,et al.  A novel endothelial-derived lipase that modulates HDL metabolism , 1999, Nature Genetics.

[12]  K. Hirata,et al.  Identification of mRNA for 5-HT1 and 5-HT2 receptor subtypes in human coronary arteries. , 1999, Cardiovascular research.

[13]  N. Maeda,et al.  Hepatic Lipase Deficiency Increases Plasma Cholesterol but Reduces Susceptibility to Atherosclerosis in Apolipoprotein E-deficient Mice* , 1997, The Journal of Biological Chemistry.

[14]  D. Rader,et al.  Unravelling high density lipoprotein-apolipoprotein metabolism in human mutants and animal models , 1996, Current opinion in lipidology.

[15]  I. Goldberg.  Lipoprotein lipase and lipolysis: central roles in lipoprotein metabolism and atherogenesis. , 1996, Journal of lipid research.

[16]  Y. Yazaki,et al.  Suppression of diet-induced atherosclerosis in low density lipoprotein receptor knockout mice overexpressing lipoprotein lipase. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[17]  M. Komaromy,et al.  Acceleration of uptake of LDL but not chylomicrons or chylomicron remnants by cells that secrete apoE and hepatic lipase. , 1994, Journal of lipid research.

[18]  G. Mcclearn,et al.  Genetic and environmental influences on serum lipid levels in twins. , 1993, The New England journal of medicine.

[19]  S. Nojima,et al.  Detergent-resistant phospholipase A1 from Escherichia coli membranes. , 1991, Methods in enzymology.

[20]  G. Schonfeld,et al.  Genetic heterogeneity of lipoproteins in inbred strains of mice: analysis by gel-permeation chromatography. , 1990, Metabolism: clinical and experimental.

[21]  L. Jorde,et al.  The inheritance of high density lipoprotein cholesterol and apolipoproteins A-I and A-II. , 1984, Atherosclerosis.

[22]  M C Hjortland,et al.  High density lipoprotein as a protective factor against coronary heart disease. The Framingham Study. , 1977, The American journal of medicine.

[23]  S B Hulley,et al.  HDL Cholesterol and Other Lipids in Coronary Heart Disease: The Cooperative Lipoprotein Phenotyping Study , 1977, Circulation.

[24]  W. J. Dyer,et al.  A rapid method of total lipid extraction and purification. , 1959, Canadian journal of biochemistry and physiology.

[25]  R. Havel,et al.  The distribution and chemical composition of ultracentrifugally separated lipoproteins in human serum. , 1955, The Journal of clinical investigation.