on January 5, 2004
Arteriosclerosis, Thrombosis, and Vascular Biology. 2004
Published online before print January 5, 2004, doi: 10.1161/01.ATV.0000115638.27381.97
Published online before print January 5, 2004, doi: 10.1161/01.ATV.0000115638.27381.97
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Submitted on October 24, 2003
Accepted on December 12, 2003
Adipophilin Enhances Lipid Accumulation and Prevents Lipid Efflux From THP-1 Macrophages: Potential Role in Atherogenesis
Guilhem Larigauderie ;
From the Department of Atherosclerosis (G.L., C.F., C.L., C.C., J.-C.F., G.C., M.R.), SERLIA-INSERM UR545, Institut Pasteur de Lille, France; and GlaxoSmithKline (M.J.), King of Prussia, PA.
* To whom correspondence should be addressed. E-mail: mustapha.rouis{at}pasteur-lille.fr.
Objective--Uptake of modified low-density lipoprotein (LDL) by macrophages through scavenger receptors results in lipid droplets accumulation and foam cell formation. Excess lipid deposition in macrophages has been reported to modulate expression of several genes including adipophilin. In this study, we investigated the function of adipophilin in lipid accumulation and cholesterol efflux in THP-1 macrophages.
Methods and Results--Adipophilin mRNA expression was 3.5-fold higher in human atherosclerotic plaques compared with healthy areas of the same arteries. Moreover, in the presence of acetylated LDL (AcLDL), triglycerides and cholesteryl esters were increased in macrophages overexpressing adipophilin by 40% and 67%, respectively, whereas their accumulation was reduced when endogenous cellular adipophilin was depleted using siRNA approach. In addition, neither overexpression nor downregulation of adipophilin altered expression of genes involved in lipid efflux. However, the affinity and the number of AcLDL receptors were not affected. After 24-hour incubation of lipid-loaded macrophages with apolipoprotein A-I, cholesterol efflux was reduced by 47% in adipophilin transfected cells versus control cells.
Conclusion--Our results showed that stimulation of adipophilin expression in macrophages by modified LDL promotes triglycerides and cholesterol storage and reduces cholesterol efflux. Therefore, adipophilin might contribute, in vivo, to lipid accumulation in the intima of the arterial wall.
Key words: adipophilin • macrophage • acetylated LDL • cholesterol efflux • atherosclerosis
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