Lipoprotein size is a main determinant for the rate of hydrolysis by exogenous LPL in human plasma |
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Authors: | Oleg Kovrov Fredrik Landfors Valeria Saar-Kovrov Ulf Näslund Gunilla Olivecrona |
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Affiliation: | 1. Department of Medical Biosciences, Umeå University, Umeå, Sweden;2. Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden;3. Department of Pathology, CARIM School for Cardiovascular Diseases MUMC+, Maastricht University, Maastricht, The Netherlands;4. Heart Centre and Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden |
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Abstract: | LPL is a key player in plasma triglyceride metabolism. Consequently, LPL is regulated by several proteins during synthesis, folding, secretion, and transport to its site of action at the luminal side of capillaries, as well as during the catalytic reaction. Some proteins are well known, whereas others have been identified but are still not fully understood. We set out to study the effects of the natural variations in the plasma levels of all known LPL regulators on the activity of purified LPL added to samples of fasted plasma taken from 117 individuals. The enzymatic activity was measured at 25°C using isothermal titration calorimetry. This method allows quantification of the ability of an added fixed amount of exogenous LPL to hydrolyze triglyceride-rich lipoproteins in plasma samples by measuring the heat produced. Our results indicate that, under the conditions used, the normal variation in the endogenous levels of apolipoprotein C1, C2, and C3 or the levels of angiopoietin-like proteins 3, 4, and 8 in the fasted plasma samples had no significant effect on the recorded activity of the added LPL. Instead, the key determinant for the LPL activity was a lipid signature strongly correlated to the average size of the VLDL particles. The signature involved not only several lipoprotein and plasma lipid parameters but also apolipoprotein A5 levels. While the measurements cannot fully represent the action of LPL when attached to the capillary wall, our study provides knowledge on the interindividual variation of LPL lipolysis rates in human plasma. |
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Keywords: | plasma triglyceride metabolism apolipoproteins angiopoietin-like proteins lipidomics isothermal titration calorimetry VLDL particle size exogenous LPL lipid signature capillaries ANGPTL" },{" #name" :" keyword" ," $" :{" id" :" kwrd0060" }," $$" :[{" #name" :" text" ," _" :" angiopoietin-like protein Apo" },{" #name" :" keyword" ," $" :{" id" :" kwrd0070" }," $$" :[{" #name" :" text" ," _" :" apolipoprotein DOC" },{" #name" :" keyword" ," $" :{" id" :" kwrd0080" }," $$" :[{" #name" :" text" ," _" :" deoxycholate GPIHBP1" },{" #name" :" keyword" ," $" :{" id" :" kwrd0090" }," $$" :[{" #name" :" text" ," _" :" glycosylphosphatidylinositol-anchored HDL-binding protein 1 HSPG" },{" #name" :" keyword" ," $" :{" id" :" kwrd0100" }," $$" :[{" #name" :" text" ," _" :" heparan sulphate proteoglycan ITC" },{" #name" :" keyword" ," $" :{" id" :" kwrd0110" }," $$" :[{" #name" :" text" ," _" :" isothermal titration calorimetry TG" },{" #name" :" keyword" ," $" :{" id" :" kwrd0120" }," $$" :[{" #name" :" text" ," _" :" triglyceride TRL" },{" #name" :" keyword" ," $" :{" id" :" kwrd0130" }," $$" :[{" #name" :" text" ," _" :" triglyceride-rich lipoprotein VIPVIZA" },{" #name" :" keyword" ," $" :{" id" :" kwrd0140" }," $$" :[{" #name" :" text" ," _" :" visualization of asymptomatic atherosclerotic disease for optimum cardiovascular prevention WAT" },{" #name" :" keyword" ," $" :{" id" :" kwrd0150" }," $$" :[{" #name" :" text" ," _" :" white adipose tissue |
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