Adipophilin enhances lipid accumulation and prevents lipid efflux from THP-1 macrophages: Potential role in atherogenesis
Adipophilin enhances lipid accumulation and prevents lipid efflux from THP-1 macrophages: Potential role in atherogenesis
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DOI：
10.1161/01.atv.0000115638.27381.97
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发表时间：
2004-03-01
影响因子：
8.7
通讯作者：
Rouis, M
中科院分区：
文献类型：
--
作者：
Larigauderie, G;Furman, C;Rouis, M
目的 - 巨噬细胞通过清道夫受体摄取修饰的低密度脂蛋白 (LDL)，导致脂滴积累和泡沫细胞形成。据报道，巨噬细胞中过量的脂质沉积可调节包括嗜脂肪蛋白在内的多种基因的表达。在本研究中，我们研究了 Adipophilin 在 THP-1 巨噬细胞中脂质积累和胆固醇流出中的功能。方法和结果 - 与相同动脉的健康区域相比，人类动脉粥样硬化斑块中 Adipophilin mRNA 表达量高 3.5 倍。此外，在乙酰化低密度脂蛋白（AcLDL）存在的情况下，过度表达亲脂蛋白的巨噬细胞中的甘油三酯和胆固醇酯分别增加了40%和67%，而当使用siRNA方法耗尽内源性细胞亲脂蛋白时，它们的积累量则减少。此外，亲脂肪蛋白的过度表达和下调都不会改变参与脂质流出的基因的表达。然而，AcLDL 受体的亲和力和数量并未受到影响。将载脂巨噬细胞与载脂蛋白 A-I 孵育 24 小时后，与对照细胞相比，亲脂蛋白转染细胞中的胆固醇外流减少了 47%。结论 - 我们的结果表明，修饰 LDL 刺激巨噬细胞中的脂蛋白表达可促进甘油三酯和胆固醇储存，并减少胆固醇外流。因此，在体内，亲脂蛋白可能有助于动脉壁内膜中的脂质积累。
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.