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 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.
Highlights
Previous studies have shown that targeted deletion of endothelial lipase (EL) markedly increases the plasma high density lipoprotein cholesterol (HDL-C) level in mice
Because HDL has been shown to inhibit expression of vascular cell adhesion molecule (VCAM)-1 induced by pro-inflammatory cytokines [20], we checked the effect of HDL-WT or HDL-ELϪ/Ϫ on the cytokine-induced vascular cell adhesion molecule-1 (VCAM-1) expression in human umbilical vein endothelial cell (HUVEC)
The VCAM-1 expression induced by tumor necrosis factor (TNF)-␣ was markedly reversed by coincubation with HDL-WT and HDL-ELϪ/Ϫ (Fig. 1A)
Summary
Previous studies have shown that targeted deletion of endothelial lipase (EL) markedly increases the plasma high density lipoprotein cholesterol (HDL-C) level in 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. To evaluate the anti-inflammatory actions of HDL in vivo, lipopolysaccharide-induced systemic inflammation was generated in these mice. Targeted deletion of endothelial lipase increases HDL particles with anti-inflammatory properties both in vitro and in vivo. HDL improves endothelial function by stimulating endothelial nitric oxide production It inhibits the expression of cell adhesion proteins such as vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1, and E-selectin, and thereby can inhibit inflammatory infiltrates accumulating in the vessel wall [2].
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