文章基本信息

标题：Endothelial lipase modulates HDL but has no effect on atherosclerosis development in apoE-/- and LDLR-/- mice
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作者：Ko, Kerry W. S. ; Paul, Antoni ; Ma, Ke 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：2005
卷号：46
期号：12
页码：2586-2594
DOI：10.1194/jlr.M500366-JLR200
出版社：American Society for Biochemistry and Molecular Biology
摘要：Endothelial lipase (EL) is a determinant of high density lipoprotein-cholesterol(HDL-C) level, which is negatively correlated with atherosclerosissusceptibility. We found no difference in aortic atheroscleroticlesion areas between 26-week-old EL^+/+ apolipoprotein E-deficient(apoE^–/–) and EL^–/– apoE^–/–mice. To more firmly establish the role of EL in atherosclerosis,we extended our study to EL^–/– and EL^+/+ low densitylipoprotein receptor-deficient (LDLR^–/–) mice thatwere fed a Western diet. Morphometric analysis again revealedno difference in atherosclerosis lesion area between the twogroups. Compared with EL^+/+ mice, we found increased HDL-C inEL^–/– mice with apoE^–/– or LDLR^–/–background but no difference in macrophage content between lesionsof EL^–/– and EL^+/+ mice in apoE^–/– orLDLR^–/– background. EL inactivation had no effecton hepatic mRNAs of proteins involved in reverse cholesteroltransport. A survey of lipid homeostasis in EL^+/+ and EL^–/–macrophages revealed that oxidized LDL-induced ABCA1 was attenuatedin EL^–/– macrophages. This potentially proatherogenicchange may have nullified any minor protective increase of HDLin EL^–/– mice. Thus, although EL modulated lipoprotein profile in mice, therewas no effect of EL inactivation on atherosclerosis developmentin two hyperlipidemic atherosclerosis-prone mouse models. Abbreviations: apoE, apolipoprotein E; EL, endothelial lipase; FPLC, fast-protein liquid chromatography; IDL, intermediate density lipoprotein; HDL-C, high density lipoprotein-cholesterol; LDLR, low density lipoprotein receptor; OxLDL, oxidized low density lipoprotein; SR-A, scavenger receptor A; SR-BI, scavenger receptor class B type I Supplementary key words atherogenesis • in vivo • immunohistochemistry • liver • macrophage • reverse cholesterol transport • inflammation • high density lipoprotein • apolipoprotein E • low density lipoprotein receptor