Targeted deletion of endothelial lipase increases HDL particles with anti-inflammatory properties both in vitro and in vivo
Targeted deletion of endothelial lipase increases HDL particles with anti-inflammatory properties both in vitro and in vivo
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DOI：
10.1194/jlr.m008417
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发表时间：
2011-01-01
影响因子：
6.5
通讯作者：
Hirata, Ken-ichi
中科院分区：
文献类型：
--
作者：
Hara, Tetsuya;Ishida, Tatsuro;Hirata, Ken-ichi
以往的研究表明，靶向缺失内皮脂酶（EL）可显著提高小鼠血浆高密度脂蛋白胆固醇（HDL-C）水平。然而，对EL抑制后HDL颗粒的功能质量知之甚少。因此，本研究评估了从EL-/-和野生型（WT）小鼠分离的HDL的功能质量。通过体外测定来评价来自EL-/-和WT小鼠的HDL的抗炎功能。从WT和EL-/-小鼠中分离的HDL的功能，如PON-1或PAF-AH活性，对精氨酸诱导的血管细胞粘附分子-1表达的抑制，对LDL氧化的抑制，以及胆固醇流出的能力在WT和EL-/-小鼠中相似。相反，HDL的脂多糖中和能力在EL-/-小鼠中显著高于WT小鼠。为了评价HDL在体内的抗炎作用，在这些小鼠中产生脂多糖诱导的全身炎症。EL-/-小鼠的存活率高于WT小鼠，炎性标志物的表达低于WT小鼠。静脉内施用从EL-/-小鼠分离的HDL显著改善WT小鼠注射脂多糖后的死亡率。总之，有针对性地破坏EL增加HDL颗粒，保留抗炎和抗动脉粥样硬化功能。因此，EL抑制将是一个有用的策略，以提高血浆中的“好”胆固醇。Hara，T.，T. Ishida，Y. Kojima，H.田中T. Yasuda，M.筱原河托和凯平田内皮脂肪酶的靶向缺失增加了具有体外和体内抗炎特性的HDL颗粒。J. Lipid Res. 2011. 52：57-67。
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.-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. 52: 57-67.