Endothelial lipase is increased by inflammation and promotes LDL uptake in macrophages.
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.
Yasuda
Tomoyuki
T
Division of Cardiovascular Medicine, Kobe University Graduate School of Medicine, Japan.
Hirata
Ken-Ichi
K
Ishida
Tatsuro
T
Kojima
Yoko
Y
Tanaka
Hanayo
H
Okada
Takeaki
T
Quertermous
Thomas
T
Yokoyama
Mitsuhiro
M
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*
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