Reduced size and macrophage content of advanced atherosclerotic lesions in mice with bone marrow specific deficiency of alpha 7 nicotinic acetylcholine receptor.
Reduced size and macrophage content of advanced atherosclerotic lesions in mice with bone marrow specific deficiency of alpha 7 nicotinic acetylcholine receptor.
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DOI：
10.1371/journal.pone.0124584
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Vazquez G
中科院分区：
文献类型：
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作者：
Lee RH;Vazquez G
在巨噬细胞中，α7烟碱乙酰胆碱受体（α 7 nAChR）调节炎性细胞因子的产生、胆固醇蓄积和脂蛋白摄取。最近，我们的实验室表明，选择性刺激α7nAChR保护巨噬细胞免于凋亡，这一作用在α 7nAChR缺陷的巨噬细胞中不存在。这些结果提示巨噬细胞α 7 nAChR在动脉粥样硬化中的潜在作用。骨髓α 7 nAChR缺失的疾病小鼠模型代表了一种有吸引力的方法来解决这些体外发现的体内相关性。然而，最近的研究集中在低密度脂蛋白受体敲除（LDLRKO）小鼠的造血功能缺陷对早期动脉粥样硬化病变的影响，产生了有争议的结果。巨噬细胞α 7 nAChR是否调节晚期病变的特征也是一个问题。在这里，我们使用LDLR敲除小鼠移植野生型或α 7 nAChR敲除动物的骨髓，以重新审视α 7 nAChR造血缺陷对早期病变的影响，并首次检查其对晚期斑块的影响。在高脂饮食8周和14周后分析主动脉窦动脉粥样硬化病变。骨髓α 7 nAChR缺陷小鼠的早期病变与对照动物无差异。然而，骨髓缺失α 7 nAChR的小鼠的晚期病变表现出尺寸、巨噬细胞含量和细胞增殖的减少。这些研究首次在疾病小鼠模型中检查了α 7 nAChR造血缺陷对晚期动脉粥样硬化病变特征的影响，并提供了新的证据，强调了巨噬细胞α 7 nAChR的潜在促动脉粥样硬化作用。
In macrophages the α7 nicotinic acetylcholine receptor (α7nAChR) modulates production of inflammatory cytokines, cholesterol accumulation and lipoprotein uptake. Recently, our laboratory showed that selective stimulation of the α7nAChR protects macrophages from apoptosis, an effect that is absent in α7nAChR-deficient macrophages. All these observations are suggestive of a potential role of macrophage α7nAChR in atherosclerosis. Mouse models of the disease with bone marrow deletion of α7nAChR represent an attractive approach to address the in vivo relevance of these in vitro findings. However, recent studies that focused on the impact of hematopoietic deficiency of α7nAChR on early atherosclerotic lesions of low density lipoprotein receptor knockout (LDLRKO) mice, yielded controversial results. The question also remained whether macrophage α7nAChR modulates the characteristics of advanced lesions. Here we used LDLR knockout mice transplanted with bone marrow from wild-type or α7nAChR knockout animals to revisit the effect of hematopoietic deficiency of α7nAChR on early lesions and to examine, for the first time, its impact on advanced plaques. Aortic sinus atherosclerotic lesions were analyzed following 8 and 14 weeks on a high fat diet. Early lesions in mice with α7nAChR deficient bone marrow were not different from those in control animals. However, advanced lesions of mice with bone marrow deletion of α7nAChR exhibited reduction in size, macrophage content and cell proliferation. These studies are the first in examining the impact of hematopoietic deficiency of α7nAChR on the characteristics of advanced atherosclerotic lesions in a mouse model of the disease and provide novel evidence underscoring a potential pro-atherogenic role of macrophage α7nAChR.
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影响因子：
15.9
作者：
Seimon, Tracie A.;Wang, Yibin;Tabas, Ira A.
通讯作者：
Tabas, Ira A.
影响因子：
3.1
作者：
Akaike, Akinori;Takada-Takatori, Yuki;Izumi, Yasuhiko
通讯作者：
Izumi, Yasuhiko
影响因子：
5
作者：
Schirmer, Stephan H.;Fledderus, Joost O.;van Royen, Niels
通讯作者：
van Royen, Niels
α-7烟碱乙酰胆碱受体在替代（M2）激活的巨噬细胞中发挥作用的证据。
影响因子：
2.5
作者：
Lee, Robert H;Vazquez, Guillermo
通讯作者：
Vazquez, Guillermo
DOI：
10.1038/nri2675
发表时间：
2010-01
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
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