Nicotine Accelerates Atherosclerosis in Apolipoprotein E-Deficient Mice by Activating α7 Nicotinic Acetylcholine Receptor on Mast Cells
Nicotine Accelerates Atherosclerosis in Apolipoprotein E-Deficient Mice by Activating α7 Nicotinic Acetylcholine Receptor on Mast Cells
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DOI：
10.1161/atvbaha.116.307264
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发表时间：
2017-01-01
影响因子：
8.7
通讯作者：
Wang, Jian'an
中科院分区：
文献类型：
--
作者：
Wang, Chen;Chen, Han;Wang, Jian'an
吸烟是动脉粥样硬化的独立危险因素。尼古丁是香烟中的成瘾成分，可诱导肥大细胞（MC）释放并促进动脉粥样硬化形成。本研究的目的是确定是否尼古丁加速动脉粥样硬化通过MC介导的机制，以及是否MC稳定剂防止这种病理processe.Approach和Results-Nicotine管理增加了载脂蛋白E缺陷（Apoe（-/-））小鼠喂养富含脂肪的饮食动脉粥样硬化病变的大小。这是伴随着增强斑块内巨噬细胞含量和脂质沉积，但减少胶原和平滑肌细胞含量。Apoe（-/-）小鼠（Apoe（-/-）Kit（W-sh/W-sh））中MC缺乏减少尼古丁诱导的动脉粥样硬化。尼古丁在体外激活骨髓来源的MC，这是抑制MC稳定剂色甘酸钠或非选择性烟碱乙酰胆碱受体阻滞剂美加明。进一步的研究表明，α 7烟碱乙酰胆碱受体是MC中尼古丁激活的靶点。尼古丁并没有改变Apoe（-/-）Kit（W-sh/W-sh）小鼠动脉粥样硬化病变的大小，该小鼠用来自Apoe（-/-）α 7 nAChR（-/-）动物的MCs重建。
Objective-Cigarette smoking is an independent risk factor for atherosclerosis. Nicotine, the addictive component of cigarettes, induces mast cell (MC) release and contributes to atherogenesis. The purpose of this study was to determine whether nicotine accelerates atherosclerosis through MC-mediated mechanisms and whether MC stabilizer prevents this pathological process.Approach and Results-Nicotine administration increased the size of atherosclerotic lesions in apolipoprotein E-deficient (Apoe(-/-)) mice fed a fat-enriched diet. This was accompanied by enhanced intraplaque macrophage content and lipid deposition but reduced collagen and smooth muscle cell contents. MC deficiency in Apoe(-/-) mice (Apoe(-/-)Kit(W-sh/W-sh)) diminished nicotine-induced atherosclerosis. Nicotine activated bone marrow-derived MCs in vitro, which was inhibited by a MC stabilizer disodium cromoglycate or a nonselective nicotinic acetylcholine receptor blocker mecamylamine. Further investigation revealed that alpha 7 nicotinic acetylcholine receptor was a target for nicotine activation in MCs. Nicotine did not change atherosclerotic lesion size of Apoe(-/-)Kit(W-sh/W-sh) mice reconstituted with MCs from Apoe(-/-)alpha 7 nAChR(-/-) animals.Conclusions-Activation of alpha 7 nicotinic acetylcholine receptor on MCs is a mechanism by which nicotine enhances atherosclerosis.