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.
Highlights
Endothelial lipase (EL) is a determinant of high density lipoprotein-cholesterol (HDL-C) level, which is negatively correlated with atherosclerosis susceptibility
We explore the role of EL in atherosclerosis by analyzing the outcome of placing targeted disruption of EL into the apolipoprotein E and low density lipoprotein receptor (LDLR) knockout mouse models of increased atherosclerosis susceptibility
Both models are characterized by hypercholesterolemia with decreased HDL compared with C57BL/6 mice, and we found increased plasma phospholipids and HDL-C levels in these animals with genetic deletion of EL, we found no difference in atherosclerosis development compared with their EL wild-type counterparts
Summary
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. 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. Endothelial lipase modulates HDL but has no effect on atherosclerosis development in apoE؊/؊ and LDLR؊/؊ mice. Inactivation of EL through gene targeting [8, 9] or functional inhibition by antibody infusion [10] demonstrated that EL can function as a key physiological regulator of HDL level, details of its role in the catabolism of apolipoprotein B-containing lipoproteins have expanded [11]
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