Effects of IKKɛ on oxidised low-density lipoprotein-induced injury in vascular endothelial cells

Heart Lung Circ. 2013 May;22(5):366-72. doi: 10.1016/j.hlc.2012.11.017. Epub 2012 Dec 20.

Abstract

Background: Oxidised low-density lipoprotein (ox-LDL) led to endothelial dysfunction, which was an initial step in the formation of atheroma. The role of IKKɛ in Ox-LDL-induced endothelial cell injury was investigated in this study.

Methods: Primary cultures of endothelial cell were identified by the immunofluorescent detection of von Willebrand's factor (vWF). Wild-type and IKKɛ knockout endothelial cells were treated with ox-LDL and effects on ultrastructural morphology were evaluated by transmission electron microscopy. Western blotting analysis was conducted to evaluate effects on IL-18, VEGF, IKKα, IKKβ, IKKɛ, p65 and p50 expression.

Results: From the ultrastructural morphology of endothelial cells and the expression of inflammatory factor such as IL-18 and VEGF, it was suggested that IKKɛ knockout endothelial cells showed less severe ox-LDL-induced injury compared to wild-type endothelial cells. Ox-LDL increased IKKɛ and phosphorylated IKKɛ expression in wild-type endothelial cells, while no significant change in IKKα and IKKβ levels was observed. Ox-LDL significantly increased the expression of p65(or p50) and phosphorylated p65(or p50) in wild-type endothelial cells, while this effect was completely blocked in IKKɛ knockout endothelial cells.

Conclusions: IKKɛ might play an important role in ox-LDL-induced injury of endothelial cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Endothelial Cells / metabolism*
  • Endothelial Cells / pathology
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / genetics
  • I-kappa B Kinase / genetics
  • I-kappa B Kinase / metabolism*
  • Interleukin-18 / biosynthesis
  • Interleukin-18 / genetics
  • Lipoproteins, LDL / metabolism*
  • Lipoproteins, LDL / pharmacology
  • Mice
  • Mice, Knockout
  • NF-kappa B p50 Subunit / genetics
  • NF-kappa B p50 Subunit / metabolism
  • Phosphorylation / drug effects
  • Phosphorylation / genetics
  • Plaque, Atherosclerotic / genetics
  • Plaque, Atherosclerotic / metabolism
  • Plaque, Atherosclerotic / pathology
  • Transcription Factor RelA / genetics
  • Transcription Factor RelA / metabolism
  • Vascular Endothelial Growth Factor A / biosynthesis
  • Vascular Endothelial Growth Factor A / genetics

Substances

  • Interleukin-18
  • Lipoproteins, LDL
  • NF-kappa B p50 Subunit
  • Rela protein, mouse
  • Transcription Factor RelA
  • Vascular Endothelial Growth Factor A
  • oxidized low density lipoprotein
  • vascular endothelial growth factor A, mouse
  • Nfkb1 protein, mouse
  • I-kappa B Kinase