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

Kerry W.S. Ko, Antoni Paul, Ke Ma, Lan Li, Lawrence Chan

Research output: Contribution to journalArticlepeer-review

67 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2586-2594
Number of pages9
JournalJournal of lipid research
Volume46
Issue number12
DOIs
StatePublished - Dec 2005

Keywords

  • Apolipoprotein E
  • Atherogenesis
  • High density lipoprotein
  • Immunohistochemistry
  • In vivo
  • Inflammation
  • Liver
  • Low density lipoprotein receptor
  • Macrophage
  • Reverse cholesterol transport

ASJC Scopus subject areas

  • Endocrinology

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