Angptl 4 deficiency improves lipid metabolism, suppresses foam cell formation and protects against atherosclerosis
Angptl 4 deficiency improves lipid metabolism, suppresses foam cell formation and protects against atherosclerosis
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DOI：
10.1016/j.bbrc.2008.12.018
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发表时间：
2009-02-20
影响因子：
3.1
通讯作者：
Araki, Eiichi
中科院分区：
文献类型：
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作者：
Adachi, Hironori;Fujiwara, Yukio;Araki, Eiichi
血管生成素样蛋白家族4（Angptl 4）已显示通过抑制脂蛋白脂肪酶（LPL）来调节脂蛋白代谢。我们产生ApoE（-/-）Angptl 4（-/-）小鼠以研究Angptl 4缺乏对脂质代谢和动脉粥样硬化的影响。与ApoE（-/-）Angptl 4（+/+）小鼠相比，ApoE（-/-）Angptl 4（-/-）小鼠的空腹和橄榄油后负载的甘油三酯（TG）水平大幅降低。与ApoE（-/-）Angptl 4（+/+）小鼠相比，ApoE（-/-）Angptl 4（-/-）小鼠中动脉粥样硬化病变大小显著减小（75 +/-12%）。从Angptl 4（-/-）小鼠分离的腹膜巨噬细胞用于研究泡沫细胞形成，与来自Angptl 4（+/+）小鼠的巨噬细胞相比，显示乙酰低密度脂蛋白（acLDL）诱导的新合成的胆固醇酯（CE）积累显著减少。因此，Angptl 4的基因敲除保护ApoE（-/-）小鼠免于动脉粥样硬化的发展和进展，并强烈抑制巨噬细胞在体外变成泡沫细胞的能力。(C)2008年爱思唯尔公司All rights reserved.
Angiopoietin-like protein family 4 (Angptl 4) has been shown to regulate lipoprotein metabolism through the inhibition of lipoprotein lipase (LPL). We generated ApoE(-/-)Angptl 4(-/-) mice to study the effect of Angptl 4 deficiency on lipid metabolism and atherosclerosis. Fasting and postolive oil-loaded triglyceride (TG) levels were largely decreased in ApoE(-/-)Angptl 4(-/-) mice compared with and ApoE(-/-)Angptl 4(+/+) mice. There was a significant (75 +/- 12%) reduction in atherosclerotic lesion size in ApoE(-/-)Angptl 4(-/-) mice compared with ApoE(-/-) Angptl 4(+/+) mice. Peritoneal macrophages, isolated from Angptl 4(-/-) mice to investigate the foam cell formation, showed a significant decrease in newly synthesized cholesteryl ester (CE) accumulation induced by acetyl low-density lipoprotein (acLDL) compared with those from Angptl 4(+/+) mice. Thus, genetic knockout of Angptl 4 protects ApoE(-/-) mice against development and progression of atherosclerosis and strongly suppresses the ability of the macrophages to become foam cells in vitro. (C) 2008 Elsevier Inc. All rights reserved.