DNA polymorphism haplotypes of the human lipoprotein lipase gene: possible association with high density lipoprotein levels

1991 ◽  
Vol 86 (6) ◽  
Author(s):  
Camilla Heizmann ◽  
Todd Kirchgessner ◽  
PeterO. Kwiterovich ◽  
JohnA. Ladias ◽  
Carol Derby ◽  
...  
Keyword(s):  
High Density Lipoprotein ◽  
Lipoprotein Lipase ◽  
Dna Polymorphism ◽  
Density Lipoprotein ◽  
High Density ◽  
Lipase Gene ◽  
Lipoprotein Lipase Gene

Higher Triglycerides, Lower High-Density Lipoprotein Cholesterol, and Higher Systolic Blood Pressure in Lipoprotein Lipase–Deficient Heterozygotes

Circulation ◽  
1996 ◽  
Vol 94 (12) ◽  
pp. 3239-3245 ◽  
Author(s):  
Dennis L. Sprecher ◽  
Betsy V. Harris ◽  
Evan A. Stein ◽  
Paul S. Bellet ◽  
Leonard M. Keilson ◽  
...  
Keyword(s):  
Blood Pressure ◽  
High Density Lipoprotein ◽  
Systolic Blood Pressure ◽  
Lipoprotein Lipase ◽  
High Density Lipoprotein Cholesterol ◽  
Density Lipoprotein ◽  
High Density ◽  
Lipoprotein Cholesterol

scholarly journals Lipoprotein lipase mediates an increase in the selective uptake of high density lipoprotein-associated cholesteryl esters by hepatic cells in culture

1998 ◽  
Vol 39 (7) ◽  
pp. 1335-1348 ◽  
Author(s):  
Franz Rinninger ◽  
Tatjana Kaiser ◽  
W. Alexander Mann ◽  
Nicolette Meyer ◽  
Heiner Greten ◽  
...  
Keyword(s):  
High Density Lipoprotein ◽  
Lipoprotein Lipase ◽  
Density Lipoprotein ◽  
High Density ◽  
Cholesteryl Esters ◽  
Selective Uptake ◽  
Cells In Culture ◽  
Hepatic Cells

scholarly journals Evidence for Two Distinct Binding Sites for Lipoprotein Lipase on Glycosylphosphatidylinositol-anchored High Density Lipoprotein-binding Protein 1 (GPIHBP1)

2015 ◽  
Vol 290 (22) ◽  
pp. 13919-13934 ◽  
Author(s):  
Mart Reimund ◽  
Mikael Larsson ◽  
Oleg Kovrov ◽  
Sergo Kasvandik ◽  
Gunilla Olivecrona ◽  
...  
Keyword(s):  
High Density Lipoprotein ◽  
Lipoprotein Lipase ◽  
Binding Sites ◽  
Binding Protein ◽  
Density Lipoprotein ◽  
High Density ◽  
Lipoprotein Binding

scholarly journals Effect of Thyroid Dysfunction on High-Density Lipoprotein Subfraction Metabolism: Roles of Hepatic Lipase and Cholesteryl Ester Transfer Protein1

1998 ◽  
Vol 83 (8) ◽  
pp. 2921-2924 ◽  
Author(s):  
K. C. B. Tan ◽  
S. W. M. Shiu ◽  
A. W. C. Kung.
Keyword(s):  
High Density Lipoprotein ◽  
Cholesteryl Ester ◽  
Lipoprotein Lipase ◽  
Thyroid Dysfunction ◽  
Hepatic Lipase ◽  
Density Lipoprotein ◽  
High Density ◽  
Free T4 ◽  
Hdl Metabolism ◽  
Hypothyroid Patients

abstract To investigate the effect of thyroid dysfunction on high-density lipoprotein (HDL) metabolism, we measured HDL subfractions, apolipoprotein A-I containing particles (LpA-I and LpA-I:A-II), and the activities of enzymes involved in the remodeling and metabolism of HDL[ namely hepatic lipase (HL), lipoprotein lipase, and cholesteryl ester transfer protein (CETP)] in 18 hyperthyroid and 17 hypothyroid patients before and after treatment. HDL was subfractionated by density gradient ultracentrifugation, and LpA-I was analyzed by electroimmunodiffusion. The major changes were found in the HDL2 subfraction and in LpA-I particles. HDL2-C and LpA-I were reduced in hyperthyroidism (P < 0.01, P < 0.05, respectively) and increased in hypothyroidism (both P < 0.05) compared with their respective euthyroid matched controls. Changes in HDL2-cholesterol were reversed after treatment in both hyper- and hypothyroid patients, and LpA-I also decreased in the hypothyroid patients after treatment. HL (P < 0.05) and CETP activities (P < 0.05) were elevated in hyperthyroidism and reduced in hypothyroidism (P < 0.05, P < 0.01 respectively) and both were related to free T4 levels. The changes in HDL2-C and LpA-I correlated significantly with changes in HL after treatment but not with CETP or lipoprotein lipase. In summary, HDL metabolism was altered in thyroid dysfunction, and the effect of thyroid hormone on HDL was mediated mainly via its effect on HL activity.

scholarly journals A lipoprotein lipase–GPI-anchored high-density lipoprotein–binding protein 1 fusion lowers triglycerides in mice: Implications for managing familial chylomicronemia syndrome

2019 ◽  
Vol 295 (10) ◽  
pp. 2900-2912 ◽  
Author(s):  
Amitabh V. Nimonkar ◽  
Stephen Weldon ◽  
Kevin Godbout ◽  
Darrell Panza ◽  
Susan Hanrahan ◽  
...  
Keyword(s):  
Fusion Protein ◽  
Enzyme Replacement Therapy ◽  
High Density Lipoprotein ◽  
Replacement Therapy ◽  
Lipoprotein Lipase ◽  
Binding Protein ◽  
Density Lipoprotein ◽  
High Density ◽  
Enzyme Replacement ◽  
Lipoprotein Binding

Lipoprotein lipase (LPL) is central to triglyceride metabolism. Severely compromised LPL activity causes familial chylomicronemia syndrome (FCS), which is associated with very high plasma triglyceride levels and increased risk of life-threatening pancreatitis. Currently, no approved pharmacological intervention can acutely lower plasma triglycerides in FCS. Low yield, high aggregation, and poor stability of recombinant LPL have thus far prevented development of enzyme replacement therapy. Recently, we showed that LPL monomers form 1:1 complexes with the LPL transporter glycosylphosphatidylinositol-anchored high-density lipoprotein–binding protein 1 (GPIHBP1) and solved the structure of the complex. In the present work, we further characterized the monomeric LPL/GPIHBP1 complex and its derivative, the LPL–GPIHBP1 fusion protein, with the goal of contributing to the development of an LPL enzyme replacement therapy. Fusion of LPL to GPIHBP1 increased yields of recombinant LPL, prevented LPL aggregation, stabilized LPL against spontaneous inactivation, and made it resistant to inactivation by the LPL antagonists angiopoietin-like protein 3 (ANGPTL3) or ANGPTL4. The high stability of the fusion protein enabled us to identify LPL amino acids that interact with ANGPTL4. Additionally, the LPL–GPIHBP1 fusion protein exhibited high enzyme activity in in vitro assays. Importantly, both intravenous and subcutaneous administrations of the fusion protein lowered triglycerides in several mouse strains without causing adverse effects. These results indicate that the LPL–GPIHBP1 fusion protein has potential for use as a therapeutic for managing FCS.

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