Macrophage Elovl6 Deficiency Ameliorates Foam Cell Formation and Reduces Atherosclerosis in Low-Density Lipoprotein Receptor-Deficient Mice
Macrophage Elovl6 Deficiency Ameliorates Foam Cell Formation and Reduces Atherosclerosis in Low-Density Lipoprotein Receptor-Deficient Mice
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DOI：
10.1161/atvbaha.110.221663
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发表时间：
2011-09-01
影响因子：
8.7
通讯作者：
Shimano, Hitoshi
中科院分区：
文献类型：
--
作者：
Saito, Ryo;Matsuzaka, Takashi;Shimano, Hitoshi
长链脂肪酸延长酶（ELovl 6）是延长饱和和单不饱和脂肪酸的限速酶，并且已经显示通过脂肪酸组成的修饰与肥胖诱导的胰岛素抵抗相关。在这项研究中，我们研究了Elov 16在巨噬细胞中的泡沫细胞形成和小鼠动脉粥样硬化中的作用。方法和结果-为了研究Elov 16在巨噬细胞中动脉粥样硬化进展中的作用，我们将野生型或Elov 16（-/-）小鼠的骨髓细胞移植到喂食西方饮食的经辐射的LDL-R（-/-）小鼠中。在Elov 16（-/-）骨髓细胞移植的LDL-R（-/-）小鼠中，主动脉粥样硬化病变面积和巨噬细胞浸润显著小于野生型。与野生型小鼠相比，Elov 16（-/-）小鼠腹腔巨噬细胞暴露于乙酰化LDL时酯化胆固醇的蓄积程度较低。Elov 16（-/-）巨噬细胞的胆固醇流出和胆固醇流出转运蛋白的表达增加，尽管两组之间没有发现乙酰化LDL的摄取差异。对巨噬细胞中酯化胆固醇组分的脂肪酸组成进行分析，发现缺乏Elov 16时，n-6多不饱和脂肪酸减少。结论-这些发现表明，Elov 16在巨噬细胞中可能有助于泡沫细胞的形成和动脉粥样硬化的进展。（Arterioscler Thromb Vasc Biol.2011;31：1973-1979.）
Objective-Elovl6, a long-chain fatty acid elongase, is a rate-limiting enzyme that elongates saturated and monounsaturated fatty acids and has been shown to be related to obesity-induced insulin resistance via modification of fatty acid composition. In this study, we investigated the roles of Elovl6 in foam cell formation in macrophages and atherosclerosis in mice.Methods and Results-To investigate the roles of Elovl6 in macrophages in the progression of atherosclerosis, we transplanted bone marrow cells of wild-type or Elovl6(-/-) mice into irradiated LDL-R(-/-) mice that were fed a western diet. Aortic atherosclerotic lesion areas and infiltration of macrophages were significantly smaller in Elovl6(-/-) bone marrow cells-transplanted LDL-R(-/-) mice than in wild-type. Accumulation of esterified cholesterol on exposure to acetylated-LDL was less severe in peritoneal macrophages from Elovl6(-/-) mice than those from wild-type. Cholesterol efflux and expression of cholesterol efflux transporters were increased in Elovl6(-/-) macrophages, although no difference in uptake of acetylated-LDL was found between the two groups. On analysis of fatty acid composition of the esterified cholesterol fraction in macrophages, n-6 polyunsaturated fatty acids were decreased by absence of Elovl6.Conclusion-These findings suggest that Elovl6 in macrophages may contribute to foam cell formation and progression of atherosclerosis. (Arterioscler Thromb Vasc Biol. 2011;31:1973-1979.)