Abstract 10941: Hepatic Overexpression of Endothelial Lipase Induces a Markedly Low HDL-Cholesterol but Maintains Macrophage Reverse Cholesterol Transport in Mice in an ABCA1-dependent Fashion
We previously showed that hepatic overexpression of endothelial lipase (EL) by adenoviral vectors markedly reduced plasma HDL levels but maintained macrophage reverse cholesterol transport (RCT) in an SR-BI-dependent fashion in mice. In the present study, we further investigated roles of ABCA1 using probucol, an ABCA1 inhibitor, under EL overexpression. In vivo RCT assay demonstrated that hepatic EL overexpression reduced macrophages-derived 3H-cholesterol in plasma, especially HDL fractions but maintained fecal 3H-cholesterol excretion as compared with the control under normal chow. Probucol diet reduced both 3H- and non-radiolabeled-cholesterol levels in HDL fraction, which were further exacerbated by EL overexpression. Interestingly, probucol diet combined with EL overexpression clearly promoted fecal excretion of macrophages-derived 3H-cholesterol, indicating that EL overexpression and ABCA1 inhibition synergistically enhanced macrophage RCT despite of extremely low HDL levels.
Author Disclosures: S. Takiguchi: None. M. Ayaori: None. H. Uto-Kondo: None. E. Yakushiji: None. K. Nakaya: None. M. Sasaki: None. T. Komatsu: None. M. Kamiyama: None. T. Nishida: None. K. Ikewaki: None.
- © 2015 by American Heart Association, Inc.