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

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.