Endothelial lipase modulates HDL but has no effect on atherosclerosis development in apoE−/− and LDLR−/− mice

Abstract

Endothelial lipase (EL) is a determinant of high density lipoprotein-cholesterol (HDL-C) level, which is negatively correlated with atherosclerosis susceptibility. We found no difference in aortic atherosclerotic lesion areas between 26-week-old EL+/+ apolipoprotein E-deficient (apoE−/−) and EL−/− apoE−/− mice. To more firmly establish the role of EL in atherosclerosis, we extended our study to EL−/− and EL+/+ low density lipoprotein receptor-deficient (LDLR−/−) mice that were fed a Western diet. Morphometric analysis again revealed no difference in atherosclerosis lesion area between the two groups. Compared with EL+/+ mice, we found increased HDL-C in EL−/− mice with apoE−/− or LDLR−/− background but no difference in macrophage content between lesions of EL−/− and EL+/+ mice in apoE−/− or LDLR−/− background. EL inactivation had no effect on hepatic mRNAs of proteins involved in reverse cholesterol transport. A survey of lipid homeostasis in EL+/+ and EL−/− macrophages revealed that oxidized LDL-induced ABCA1 was attenuated in EL−/− macrophages. This potentially proatherogenic change may have nullified any minor protective increase of HDL in EL−/− mice.Thus, although EL modulated lipoprotein profile in mice, there was no effect of EL inactivation on atherosclerosis development in two hyperlipidemic atherosclerosis-prone mouse models.

Keywords

• atherogenesis
• in vivo
• immunohistochemistry
• liver
• macrophage
• reverse cholesterol transport