Macrophage adipose triglyceride lipase deficiency attenuates atherosclerotic lesion development in low-density lipoprotein receptor knockout mice.
Macrophage adipose triglyceride lipase deficiency attenuates atherosclerotic lesion development in low-density lipoprotein receptor knockout mice.
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DOI：
10.1161/atvbaha.110.215814
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发表时间：
2011-01
期刊：
影响因子：
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通讯作者：
Kratky D
中科院分区：
文献类型：
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作者：
Lammers B;Chandak PG;Aflaki E;Van Puijvelde GH;Radovic B;Hildebrand RB;Meurs I;Out R;Kuiper J;Van Berkel TJ;Kolb D;Haemmerle G;Zechner R;Levak-Frank S;Van Eck M;Kratky D
巨噬细胞甘油三酯（TG）积累对动脉粥样硬化的影响迄今尚未得到详细研究。脂肪甘油三酯脂肪酶（ATGL）是TG水解初始阶段的限速酶。由于ATGL敲除（KO）小鼠在巨噬细胞中表现出大量TG积累，我们使用ATGL KO小鼠来研究巨噬细胞TG积累对动脉粥样硬化的影响。低密度脂蛋白受体（LDLr） KO小鼠移植ATGL KO （ATGL KO→LDLr KO）或野生型（野生型→LDLr KO）小鼠的骨髓，用Western-type饮食攻毒9周。尽管ATGL KO巨噬细胞中有TG积累，但ATGL KO→LDLr KO小鼠的动脉粥样硬化减少43%，与血浆MCP-1和巨噬细胞白细胞介素-6浓度降低相关。这与巨噬细胞数量减少相吻合，可能是因为斑块内凋亡增加39%，ATGL KO巨噬细胞的迁移能力下降。白细胞数量的减少可能是由于Lin - Sca-1+cKit+造血干细胞群减少了36%。我们得出结论，ATGL KO→LDLr KO小鼠动脉粥样硬化的衰减是由于炎症性巨噬细胞向动脉壁的浸润减少和巨噬细胞凋亡增加。
The consequences of macrophage triglyceride (TG) accumulation on atherosclerosis have not been studied in detail so far. Adipose triglyceride lipase (ATGL) is the rate-limiting enzyme for the initial step in TG hydrolysis. Because ATGL knockout (KO) mice exhibit massive TG accumulation in macrophages, we used ATGL KO mice to study the effects of macrophage TG accumulation on atherogenesis. Low-density lipoprotein receptor (LDLr) KO mice were transplanted with bone marrow from ATGL KO (ATGL KO→LDLr KO) or wild-type (wild-type→LDLr KO) mice and challenged with a Western-type diet for 9 weeks. Despite TG accumulation in ATGL KO macrophages, atherosclerosis in ATGL KO→LDLr KO mice was 43% reduced associated with decreased plasma MCP-1 and macrophage interleukin-6 concentrations. This coincided with a reduced amount of macrophages, possibly because of a 39% increase in intraplaque apoptosis and a decreased migratory capacity of ATGL KO macrophages. The reduced number of white blood cells might be due to a 36% decreased Lin−Sca-1+cKit+ hematopoietic stem cell population. We conclude that the attenuation of atherogenesis in ATGL KO→LDLr KO mice is due to decreased infiltration of less inflammatory macrophages into the arterial wall and increased macrophage apoptosis.