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 athero-sclerosis-prone mouse models. - Ko, K. W. S., A. Paul, K. Ma, L. Li, and L. Chan. Endothelial lipase modulates HDL but has no effect on atherosclerosis development in apoE (+ / +) and LDLR (- / -) mice.