文章基本信息

标题：Targeted deletion of endothelial lipase increases HDL particles with anti-inflammatory properties both in vitro and in vivo
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作者：Tetsuya Hara ; Tatsuro Ishida ; Yoko Kojima 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：2011
卷号：52
期号：1
页码：57-67
DOI：10.1194/jlr.M008417
语种：English
出版社：American Society for Biochemistry and Molecular Biology
摘要：Previous studies have shown that targeted deletion of endothelial lipase (EL) markedly increases the plasma high density lipoprotein cholesterol (HDL-C) level in mice. However, little is known about the functional quality of HDL particles after EL inhibition. Therefore, the present study assessed the functional quality of HDL isolated from EL ^−/− and wild-type (WT) mice. Anti-inflammatory functions of HDL from EL ^−/− and WT mice were evaluated by in vitro assays. The HDL functions such as PON-1 or PAF-AH activities, inhibition of cytokine-induced vascular cell adhesion molecule-1 expression, inhibition of LDL oxidation, and the ability of cholesterol efflux were similar in HDL isolated from WT and EL ^−/− mice. In contrast, the lipopolysaccharide-neutralizing capacity of HDL was significantly higher in EL ^−/− mice than that in WT mice. To evaluate the anti-inflammatory actions of HDL in vivo, lipopolysaccharide-induced systemic inflammation was generated in these mice. EL ^−/− mice showed higher survival rate and lower expression of inflammatory markers than WT mice. Intravenous administration of HDL isolated from EL ^−/− mice significantly improved the mortality after lipopolysaccharide injection in WT mice. In conclusion, targeted disruption of EL increased HDL particles with preserved anti-inflammatory and anti-atherosclerotic functions. Thus, EL inhibition would be a useful strategy to raise ‘good’ cholesterol in the plasma.
关键词：high density lipoprotein ; inflammation ; lipopolysaccharide ; endotoxin shock ; adhesion molecule