α7 Nicotinic Acetylcholine Receptor Is Expressed in Human Atherosclerosis and Inhibits Disease in Mice-Brief Report
α7 Nicotinic Acetylcholine Receptor Is Expressed in Human Atherosclerosis and Inhibits Disease in Mice-Brief Report
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DOI：
10.1161/atvbaha.114.303892
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发表时间：
2014-12-01
影响因子：
8.7
通讯作者：
Hansson, Goran K.
中科院分区：
文献类型：
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作者：
Johansson, Maria E.;Ulleryd, Marcus A.;Hansson, Goran K.
已知自主神经系统的胆碱能途径调节炎症。由于动脉粥样硬化是一种慢性炎症状态，我们测试了胆碱能信号是否在这种疾病中起作用。我们分析了α 7烟碱乙酰胆碱受体（α 7 nAChR）在人类动脉粥样硬化斑块的表达，并研究了其对高胆固醇血症Ldlr（-/-）小鼠模型中动脉粥样硬化发展的影响。方法和结果-α 7 nAChR蛋白在人类动脉粥样硬化斑块的手术标本中的T细胞和巨噬细胞上检测到。为了研究α 7 nAChR信号在动脉粥样硬化中的作用，对雄性Ldlr（-/-）小鼠进行致死性照射，并用野生型或α 7 nAChR缺陷动物的骨髓重建。造血细胞α 7 nAChR的消融增加了72%的主动脉粥样硬化。这是伴随着主动脉干扰素-γ mRNA的增加，这意味着增加的Th 1活性在a7 nAChR signaling. Conclusions的情况下，本研究表明，通过造血α 7 nAChR信号抑制动脉粥样硬化，并表明它通过调节免疫炎症。鉴于观察到α 7 nAChR由人类斑块中的T细胞和巨噬细胞表达，我们的研究结果支持胆碱能调节也可以抑制人类疾病发展的观点。
Objective-Cholinergic pathways of the autonomic nervous system are known to modulate inflammation. Because atherosclerosis is a chronic inflammatory condition, we tested whether cholinergic signaling operates in this disease. We have analyzed the expression of the alpha 7 nicotinic acetylcholine receptor (alpha 7nAChR) in human atherosclerotic plaques and studied its effects on the development of atherosclerosis in the hypercholesterolemic Ldlr(-/-) mouse model.Approach and Results-alpha 7nAChR protein was detected on T cells and macrophages in surgical specimens of human atherosclerotic plaques. To study the role of alpha 7nAChR signaling in atherosclerosis, male Ldlr(-/-) mice were lethally irradiated and reconstituted with bone marrow from wild-type or alpha 7nAChR-deficient animals. Ablation of hematopoietic cell alpha 7nAChR increased aortic atherosclerosis by 72%. This was accompanied by increased aortic interferon-gamma mRNA, implying increased Th1 activity in the absence of a7nAChR signaling.Conclusions-The present study shows that signaling through hematopoietic alpha 7nAChR inhibits atherosclerosis and suggests that it operates by modulating immune inflammation. Given the observation that alpha 7nAChR is expressed by T cells and macrophages in human plaques, our findings support the notion that cholinergic regulation may act to inhibit disease development also in man.