title: Endothelial lipase is increased by inflammation and promotes LDL uptake in macrophages.
abstract: OBJECTIVE
  Endothelial lipase (EL) is a member of the lipoprotein lipase family that regulates HDL metabolism. EL is known to act as a bridging molecule for monocytes or lipoproteins in vascular endothelial cells. We investigated the role and regulatory mechanisms of EL expression in macrophages.
  
  
  METHODS
  Macrophages originating from wild-type (EL+/+) and EL-deficient (EL-/-) mice were stimulated with lipopolysaccharide (LPS). The expression of EL mRNA was evaluated by northern blotting. DiI-LDL was used to measure the uptake of native low-density lipoprotein (nLDL).
  
  
  RESULTS
  LPS increased EL mRNA levels by increasing intracellular oxidative stress in the macrophages. LPS did not affect EL expression in macrophages derived from Toll-like receptor 4 (TLR4) gene mutant mice, C3H/HeJ. The uptake of nLDL after LPS-treatment was significantly lower in macrophages from EL-/- mice than those from EL+/+ mice. Simvastatin suppressed the LPS-induced upregulation of EL expression and uptake of nLDL.
  
  
  CONCLUSIONS
  EL expression is upregulated by LPS via TLR4 and promotes the uptake of nLDL by macrophages. Simvastatin inhibits the LPS-induced up-regulation and uptake in macrophages. Thus, our findings provide a novel role for EL in lipoprotein metabolism and would expand the range of anti-atherogenic effects of statins.
authors.affiliation: Division of Cardiovascular Medicine, Kobe University Graduate School of Medicine, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Yasuda
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Hirata
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Ishida
authors.forename: Yoko
authors.initials: Y
authors.lastname: Kojima
authors.forename: Hanayo
authors.initials: H
authors.lastname: Tanaka
authors.forename: Takeaki
authors.initials: T
authors.lastname: Okada
authors.forename: Thomas
authors.initials: T
authors.lastname: Quertermous
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Yokoyama
mesh_terms: D000818:Animals; D008078:Cholesterol, LDL / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000201:enzymology / Q000276:immunology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000276:immunology; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D008049:Lipase / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000276:immunology; D017382:Reactive Oxygen Species / Q000378:metabolism; D019821:Simvastatin / Q000494:pharmacology; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014657:Vasculitis / Q000276:immunology* / Q000378:metabolism*
chemical_list: D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008070:Lipopolysaccharides; D017382:Reactive Oxygen Species; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D019821:Simvastatin; D008049:Lipase; C498741:Lipg protein, mouse