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烟碱致动脉粥样硬化的N胆碱受体信号通路

刘佃花 张恩晖 刘冲 范博士 蔡国君

刘佃花, 张恩晖, 刘冲, 范博士, 蔡国君. 烟碱致动脉粥样硬化的N胆碱受体信号通路[J]. 药学实践与服务, 2014, 32(2): 81-84. doi: 10.3969/j.issn.1006-0111.2014.02.001
引用本文: 刘佃花, 张恩晖, 刘冲, 范博士, 蔡国君. 烟碱致动脉粥样硬化的N胆碱受体信号通路[J]. 药学实践与服务, 2014, 32(2): 81-84. doi: 10.3969/j.issn.1006-0111.2014.02.001
LIU Dianhua, ZHANG Enhui, LIU Chong, FAN Boshi, CAI Guojun. Signaling pathway of acetylcholine receptors in atherosclerosis induced by nicotinic[J]. Journal of Pharmaceutical Practice and Service, 2014, 32(2): 81-84. doi: 10.3969/j.issn.1006-0111.2014.02.001
Citation: LIU Dianhua, ZHANG Enhui, LIU Chong, FAN Boshi, CAI Guojun. Signaling pathway of acetylcholine receptors in atherosclerosis induced by nicotinic[J]. Journal of Pharmaceutical Practice and Service, 2014, 32(2): 81-84. doi: 10.3969/j.issn.1006-0111.2014.02.001

烟碱致动脉粥样硬化的N胆碱受体信号通路

doi: 10.3969/j.issn.1006-0111.2014.02.001
基金项目: 国家自然科学基金(81273503).

Signaling pathway of acetylcholine receptors in atherosclerosis induced by nicotinic

  • 摘要: 动脉粥样硬化是一种血管炎症性疾病。烟碱(尼古丁)是香烟的主要成分之一,是许多心血管疾病(如动脉粥样硬化)的致病危险因素。最近的研究表明,烟碱可与细胞表面的烟碱型乙酰胆碱受体(nAChR)高度结合并加速动脉粥样硬化的发展,nAChR在血管的各类细胞中都有不同量的表达。因此,本综述总结nAChR及配体在烟碱致动脉粥样硬化的发病机制中的作用,以及基于nAChR的信号通路在相关细胞 (如血管平滑肌细胞、内皮细胞、血小板及免疫细胞)中对动脉粥样硬化的作用,同时讨论这些通路是如何影响斑块的稳定和发展的。最后将讨论nAChR作为治疗动脉粥样硬化分子靶点的可能性。
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    [2] Doyle B, Caplice N. Plaque neovascularization and antiangiogenic therapy for atherosclerosis[J].J Am Coll Cardiol, 2007,49(21):2073-2080.
    [3] Unverdorben M, von Holt K, Winkelmann BR. Smoking and atherosclerotic cardiovascular disease:PartⅡ:role of cigarette smoking in cardiovascular disease development[J].Biomark Med, 2009,3(5):617-653.
    [4] Santanam N, Thornhill BA, Lau JK, et al. Nicotinic acetylcholine receptor signaling in atherogenesis[J].Atherosclerosis, 2012;225:264-273.
    [5] Egleton RD, Brown KC, Dasgupta P. Angiogenic activity of nicotinic acetylcholine receptors:implications in tobacco-related vascular diseases[J].Pharmacol Ther, 2009,121(2):205-223.
    [6] Ulloa L. The vagus nerve and the nicotine anti-inflammatory pathway[J].Nat Rev, 2005,4:673-684.
    [7] Cucina A, Fuso A, Coluccia P, et al. Nicotine inhibits apoptosis and stimulates proliferation in aortic smooth muscle cells through a functional nicotinic acetylcholine receptor[J].J Surg Res, 2008,150(2):227-235.
    [8] Strohschneider T, Oberhoff M, Hanke H, et al. Effect of chronic nicotine delivery on the proliferation rate of endothelial and smooth muscle cells in experimentally induced vascular wall plaques[J].Clin Invest, 1994,72(11):908-912.
    [9] Heeschen C, Jang JJ, Weis M, et al. Nicotine stimulates angiogenesis and promotes tumor growth and atherosclerosis[J].Nat Med, 2001,7(7):833-839.
    [10] Lau PP, Li L, Merched AJ, Zhang AL, et al. Nicotine induces proinflammatory responses in macrophages and the aorta leading to acceleration of atherosclerosis in low-density lipoprotein receptor(-/-) mice[J].Arterioscler Thromb Vasc Biol, 2006,26(1):143-149.
    [11] Thorgeirsson TE, Geller F, Sulem P, et al. A variant associated with nicotine dependence, lung cancer and peripheral arterial diseas[J].Nature, 2008,452(7187):638-642.
    [12] Wang Z, Wu W, et al. NF-ΚB pathway mediates vascular smooth muscle response to nicotine[J].Int J Biochem Cell Biol, 2012,45 (2):375-383.
    [13] Chan SM, Ermann J, Su L, et al. Protein microarrays for multiplex analysis of signal transduction pathways[J].Nat Med, 2004,10(12),1390-1396.
    [14] Wu JC, Chruscinski A, De Jesus Perez VA, et al. Cholinergic modulation of angiogenesis:role of the 7 nicotinic acetylcholine receptor[J].J Cell Biochem, 2009, 108(2):433-446.
    [15] Kanda Y, Watanabe Y. Nicotine-induced vascular endothelial growth factor release via the egfrerk pathway in rat vascular smooth muscle cells[J].Life Sci, 2007, 80(15):1409-1414.
    [16] Bucerius J, Manka C, Schmaljohann J, et al. Feasibility of [18F]-2-fluuoro-A85380-PET imaging of human vascular nicotinic acetylcholine receptors in vivo[J].JACC Cardiovasc Imaging, 2012,5(5):528-536.
    [17] Cooke JP. Imaging vascular nicotine receptors:a new window onto vascular disease[J].JACC Cardiovasc Imaging, 2012,5(5):537-539.
    [18] Zhang G, Marshall AL, Thomas AL, et al. In vivo knockdown of nicotinic acetylcholine receptor alpha1 diminishes aortic atherosclerosis[J].Atherosclerosis, 2011,215(1):34-42.
    [19] Li S, Zhao T, Xin H, et al. Nicotinic acetylcholine receptor alpha7 subunit mediates migration of vascular smooth muscle cells toward nicotine[J].J Pharmacol Sci, 2004,94(3):334-338.
    [20] Cooke JP, Ghebremariam YT. Endothelial nicotinic acetylcholine receptors and angiogenesis[J].Trends Cardiovas Med, 2008, 18(7):247-253.
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  • 收稿日期:  2013-07-28
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烟碱致动脉粥样硬化的N胆碱受体信号通路

doi: 10.3969/j.issn.1006-0111.2014.02.001
    基金项目:  国家自然科学基金(81273503).

摘要: 动脉粥样硬化是一种血管炎症性疾病。烟碱(尼古丁)是香烟的主要成分之一,是许多心血管疾病(如动脉粥样硬化)的致病危险因素。最近的研究表明,烟碱可与细胞表面的烟碱型乙酰胆碱受体(nAChR)高度结合并加速动脉粥样硬化的发展,nAChR在血管的各类细胞中都有不同量的表达。因此,本综述总结nAChR及配体在烟碱致动脉粥样硬化的发病机制中的作用,以及基于nAChR的信号通路在相关细胞 (如血管平滑肌细胞、内皮细胞、血小板及免疫细胞)中对动脉粥样硬化的作用,同时讨论这些通路是如何影响斑块的稳定和发展的。最后将讨论nAChR作为治疗动脉粥样硬化分子靶点的可能性。

English Abstract

刘佃花, 张恩晖, 刘冲, 范博士, 蔡国君. 烟碱致动脉粥样硬化的N胆碱受体信号通路[J]. 药学实践与服务, 2014, 32(2): 81-84. doi: 10.3969/j.issn.1006-0111.2014.02.001
引用本文: 刘佃花, 张恩晖, 刘冲, 范博士, 蔡国君. 烟碱致动脉粥样硬化的N胆碱受体信号通路[J]. 药学实践与服务, 2014, 32(2): 81-84. doi: 10.3969/j.issn.1006-0111.2014.02.001
LIU Dianhua, ZHANG Enhui, LIU Chong, FAN Boshi, CAI Guojun. Signaling pathway of acetylcholine receptors in atherosclerosis induced by nicotinic[J]. Journal of Pharmaceutical Practice and Service, 2014, 32(2): 81-84. doi: 10.3969/j.issn.1006-0111.2014.02.001
Citation: LIU Dianhua, ZHANG Enhui, LIU Chong, FAN Boshi, CAI Guojun. Signaling pathway of acetylcholine receptors in atherosclerosis induced by nicotinic[J]. Journal of Pharmaceutical Practice and Service, 2014, 32(2): 81-84. doi: 10.3969/j.issn.1006-0111.2014.02.001
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