Endothelial Lipase is Increased by Inflammation and Promotes LDL Uptake in Macrophages

• Published in: Journal of Atherosclerosis and Thrombosis Vol. 14; no. 4; pp. 192 - 201
• Main Authors: Yasuda, Tomoyuki, Hirata, Ken-ichi, Ishida, Tatsuro, Kojima, Yoko, Tanaka, Hanayo, Okada, Takeaki, Quertermous, Thomas, Yokoyama, Mitsuhiro
• Format: Journal Article
• Language: English
• Published: Japan Japan Atherosclerosis Society 2007
• Subjects: Animals; Cholesterol, LDL - metabolism; Endothelium, Vascular - enzymology; Endothelium, Vascular - immunology; Gene Expression Regulation, Enzymologic - drug effects; Gene Expression Regulation, Enzymologic - immunology; Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology; Lipase; Lipase - genetics; Lipase - metabolism; Lipopolysaccharides - pharmacology; Lipoprotein; Macrophage; Macrophages - drug effects; Macrophages - immunology; Macrophages - metabolism; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Oxidative Stress - immunology; Reactive Oxygen Species - metabolism; Simvastatin - pharmacology; Statin; Toll-Like Receptor 4 - metabolism; Vasculitis - immunology; Vasculitis - metabolism
• ISSN: 1340-3478; 1880-3873
• DOI: 10.5551/jat.E502

Aim: 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.