FoxO4 inhibits atherosclerosis through its function in bone marrow derived cells.
FoxO4 inhibits atherosclerosis through its function in bone marrow derived cells.
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DOI：
10.1016/j.atherosclerosis.2011.09.038
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发表时间：
2011-12
期刊：
影响因子：
5.3
通讯作者：
Liu, Zhi-Ping
中科院分区：
文献类型：
--
作者：
Zhu, Min;Zhang, Qing-Jun;Wang, Lin;Li, Hao;Liu, Zhi-Ping
FoxO蛋白是参与多种细胞过程的转录因子，包括免疫细胞稳态、细胞因子产生、抗氧化应激和细胞增殖和分化。尽管这些过程与动脉粥样硬化的发展有关，但对FoxO蛋白在动脉粥样硬化中的作用知之甚少。我们的目的是确定FoxO家族成员Foxo4的失活是否以及如何在体内促进动脉粥样硬化。载脂蛋白e缺乏（apoE−/−）小鼠与缺乏Foxo4 （Foxo4−/−）的动物杂交。高脂饮食（HFD） 10周后，与apoE - / -小鼠相比，Foxo4 - / - apoE - / -小鼠表现出动脉粥样硬化升高，斑块中巨噬细胞和T细胞数量增加。用野生型或Foxo4- / -骨髓重建的嵌合C57B/6小鼠的骨髓移植表明，骨髓来源细胞中Foxo4的缺乏充分促进了动脉粥样硬化。foxo4缺失的巨噬细胞对脂多糖产生炎性细胞因子IL-6和活性氧（ROS）水平升高的反应。与apoE−/−小鼠相比，hfd喂养的Foxo4−/−apoE−/−小鼠血清IL-6水平上调。FoxO4通过骨髓源性细胞抑制动脉粥样硬化，可能是通过抑制ROS和炎症细胞因子促进单核细胞募集和/或保留。
FoxO proteins are transcription factors involved in varieties of cellular processes, including immune cell homeostasis, cytokine production, anti-oxidative stress, and cell proliferation and differentiation. Although these processes are implicated in the development of atherosclerosis, very little is known about the role of FoxO proteins in the context of atherosclerosis. Our objectives were to determine whether and how inactivation of Foxo4, a member of the FoxO family, in vivo promotes atherosclerosis. Apolipoprotein E-deficient (apoE−/−) mice were crossbred with animals lacking Foxo4 (Foxo4−/−). After 10 weeks on a high fat diet (HFD), Foxo4−/−apoE−/− mice showed elevated atherosclerosis and increased amount of macrophages and T cells in the plaque compared to apoE−/− mice. Bone marrow transplantations of chimeric C57B/6 mice reconstituted with either wild-type or Foxo4−/− bone marrows indicate that Foxo4-deficiency in bone marrow derived cells sufficiently promoted atherosclerosis. Foxo4-null macrophages produced elevated inflammatory cytokine IL-6 and levels of reactive oxygen species (ROS) in response to lipopolysaccharides in vitro. Serum levels of IL-6 were upregulated in HFD-fed Foxo4−/−apoE−/− mice compared to those of apoE−/− mice. FoxO4 inhibits atherosclerosis through bone marrow derived cells, possibly by inhibition of ROS and inflammatory cytokines that promote monocyte recruitment and/or retention.
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影响因子：
30.5
作者：
通讯作者：
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影响因子：
11.8
作者：
Liu, ZP;Wang, ZG;Olson, EN
通讯作者：
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DOI：
10.1161/01.atv.14.1.133
发表时间：
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期刊：
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影响因子：
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作者：
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