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

Abstract

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 effl ux 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-infl ammatory actions of HDL in vivo, lipopolysaccharide- induced systemic infl ammation was generated in these mice. EL -/- mice showed higher survival rate and lower expression of infl ammatory 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-infl ammatory and anti-atherosclerotic functions. Thus, EL inhibition would be a useful strategy to raise 'good' cholesterol in the plasma. -Hara, T., T. Ishida, Y. Kojima, H. Tanaka, T. Yasuda, M. Shinohara, R. Toh, and K-i. Hirata. Targeted deletion of endothelial lipase increases HDL particles with anti-inflammatory properties both in vitro and in vivo. J. Lipid Res. © 2011 by the American Society for Biochemistry and Molecular Biology, Inc.