Kinetic analysis of thermal stability of human low density lipoproteins: a model for LDL fusion in atherogenesis.
نویسندگان
چکیده
Fusion of modified LDL in the arterial wall promotes atherogenesis. Earlier we showed that thermal denaturation mimics LDL remodeling and fusion, and revealed kinetic origin of LDL stability. Here we report the first quantitative analysis of LDL thermal stability. Turbidity data show sigmoidal kinetics of LDL heat denaturation, which is unique among lipoproteins, suggesting that fusion is preceded by other structural changes. High activation energy of denaturation, E(a) = 100 ± 8 kcal/mol, indicates disruption of extensive packing interactions in LDL. Size-exclusion chromatography, nondenaturing gel electrophoresis, and negative-stain electron microscopy suggest that LDL dimerization is an early step in thermally induced fusion. Monoclonal antibody binding suggests possible involvement of apoB N-terminal domain in early stages of LDL fusion. LDL fusion accelerates at pH < 7, which may contribute to LDL retention in acidic atherosclerotic lesions. Fusion also accelerates upon increasing LDL concentration in near-physiologic range, which likely contributes to atherogenesis. Thermal stability of LDL decreases with increasing particle size, indicating that the pro-atherogenic properties of small dense LDL do not result from their enhanced fusion. Our work provides the first kinetic approach to measuring LDL stability and suggests that lipid-lowering therapies that reduce LDL concentration but increase the particle size may have opposite effects on LDL fusion.
منابع مشابه
Kinetic Analysis of Thermal Stability of Human Low-Density Lipoproteins: A Model for LDL Fusion in Atherogenesis 7/19/2012 Running title: Kinetic Stability and Fusion of LDL
متن کامل
Effect of Ubiquinol-10 on the Affinity of LDL to Its Receptor: A Model for Prevention of Atherogenesis
The affinity of low density lipoprotein(LDL) to its receptor is very important, because most of LDL-uptake pathway is done by the LDL receptor and the change in size of LDL particle and the modification in its components may affect the LDL affinity for its receptor. In this study, the effects of a powerful lipid-soluble antioxidant “ubiquinol-10” have been investigated on the affinity of LDL to...
متن کاملThe Effects of Lipophilic Antioxidants on the Affinity of LDL to Its Receptor: A Model for Prevention of Atherogenesis
The affinity of low density lipoprotein (LDL) to its receptor is very important, because most of LDL-uptake pathway is done by the LDL receptor and the change in size of LDL particle and the modification in its components may affects the LDL affinity for its receptor. In this study, the effects of lipophilic agents such as vitamin E and seven volatile oils: anethol, eugenol, geraniol, limonene,...
متن کاملAggregation and fusion of low-density lipoproteins in vivo and in vitro.
Low-density lipoproteins (LDLs, also known as 'bad cholesterol') are the major carriers of circulating cholesterol and the main causative risk factor of atherosclerosis. Plasma LDLs are 20- to 25-nm nanoparticles containing a core of cholesterol esters surrounded by a phospholipid monolayer and a single copy of apolipoprotein B (550 kDa). An early sign of atherosclerosis is the accumulation of ...
متن کاملEffect of Ubiquinol-10 on the Affinity of LDL to Its Receptor: A Model for Prevention of Atherogenesis
The affinity of low density lipoprotein(LDL) to its receptor is very important, because most of LDL-uptake pathway is done by the LDL receptor and the change in size of LDL particle and the modification in its components may affect the LDL affinity for its receptor. In this study, the effects of a powerful lipid-soluble antioxidant “ubiquinol-10” have been investigated on the affinity of LDL to...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Journal of lipid research
دوره 53 10 شماره
صفحات -
تاریخ انتشار 2012