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
