文章基本信息

标题：Kinetic analysis of thermal stability of human low density lipoproteins: a model for LDL fusion in atherogenesis
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作者：Mengxiao Lu ; Donald L. Gantz ; Haya Herscovitz 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2012
卷号：53
期号：10
页码：2175-2185
DOI：10.1194/jlr.M029629
语种：English
出版社：American Society for Biochemistry and Molecular Biology
摘要：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
关键词：LDL aggregation, fusion, and rupture ; sigmoidal denaturation kinetics ; LDL subclasses ; acidic pH ; high-order reaction ; lipid-lowering therapies ; atherosclerosis