Targeted deletion of endothelial lipase increases HDL particles with anti-inflammatory properties both in vitro and in vivo

• Main Authors: Tetsuya Hara, Tatsuro Ishida, Yoko Kojima, Hanayo Tanaka, Tomoyuki Yasuda, Masakazu Shinohara, Ryuji Toh, Ken-ichi Hirata
• Format: Article
• Language: English
• Published: Elsevier 2011-01-01
• Series: Journal of Lipid Research
• Subjects: high density lipoprotein; inflammation; lipopolysaccharide; endotoxin shock; adhesion molecule
• Online Access: http://www.sciencedirect.com/science/article/pii/S0022227520404961

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.