Nicotine accelerates atherosclerosis in Apolipoprotein E-deficient mice by activating α7 nicotinic acetylcholine receptor on mast cells

Chen Wang; Han Chen; Wei Zhu; Yinchuan Xu; Mingfei Liu; Lianlian Zhu; Fan Yang; Ling Zhang; Xianbao Liu; Zhiwei Zhong; Jing Zhao; Jun Jiang; Meixiang Xiang; Hong Yu; Xinyang Hu; Hong Lu; Jian'an Wang

doi:10.1161/ATVBAHA.116.307264

Nicotine accelerates atherosclerosis in Apolipoprotein E-deficient mice by activating α7 nicotinic acetylcholine receptor on mast cells

Chen Wang, Han Chen, Wei Zhu, Yinchuan Xu, Mingfei Liu, Lianlian Zhu, Fan Yang, Ling Zhang, Xianbao Liu, Zhiwei Zhong, Jing Zhao, Jun Jiang, Meixiang Xiang, Hong Yu, Xinyang Hu, Hong Lu, Jian'an Wang

Physiology

Research output: Contribution to journal › Article › peer-review

41 Scopus citations

Abstract

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 α7 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 -/- α7nAChR -/- animals. Conclusions - Activation of α7 nicotinic acetylcholine receptor on MCs is a mechanism by which nicotine enhances atherosclerosis.

Original language	English
Pages (from-to)	53-65
Number of pages	13
Journal	Arteriosclerosis, Thrombosis, and Vascular Biology
Volume	37
Issue number	1
DOIs	https://doi.org/10.1161/ATVBAHA.116.307264
State	Published - Jan 1 2017

Bibliographical note

Funding Information:
This work was supported by the National Basic Research Program of China (973 Program, 2014CB965103), the National High-tech R&D 863 Program (no. 2013AA020101 for X. Hu, no. 2015AA020922 for X. Liu), grants from National Natural Science Foundation of China (no. 81320108003 and 31371498 for J. Wang, no. 81370247 for X. Hu, no. 81570233 for X. Liu, no. 81500334 for H. Chen, no. 81470384 and 81270179 for M. Xiang, no. 81573641 for L. Zhang, no. 81100141 for J. Jiang), the Qianjiang Talents Project of Science and Technology Department of Zhejiang Province (no. 2013R10032 for H. Chen and no. LY16H280003 for L. Zhang), the Natural Science Foundation of Zhejiang Province (no. LQ16H020004 for H. Chen), and the Fundamental Research Funds for the Central Universities (no. 2016XZZX002-03 for X. Hu).

Publisher Copyright:
© 2016 American Heart Association, Inc.

Keywords

apolipoprotein E
atherosclerosis
hypercholesterolemia
mast cell
nicotine

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine

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10.1161/ATVBAHA.116.307264

Cite this

Wang, C., Chen, H., Zhu, W., Xu, Y., Liu, M., Zhu, L., Yang, F., Zhang, L., Liu, X., Zhong, Z., Zhao, J., Jiang, J., Xiang, M., Yu, H., Hu, X., Lu, H., & Wang, J. (2017). Nicotine accelerates atherosclerosis in Apolipoprotein E-deficient mice by activating α7 nicotinic acetylcholine receptor on mast cells. Arteriosclerosis, Thrombosis, and Vascular Biology, 37(1), 53-65. https://doi.org/10.1161/ATVBAHA.116.307264

@article{302a7ddea3324e2b827953d89f71d678,

title = "Nicotine accelerates atherosclerosis in Apolipoprotein E-deficient mice by activating α7 nicotinic acetylcholine receptor on mast cells",

abstract = "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 α7 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 -/- α7nAChR -/- animals. Conclusions - Activation of α7 nicotinic acetylcholine receptor on MCs is a mechanism by which nicotine enhances atherosclerosis.",

keywords = "apolipoprotein E, atherosclerosis, hypercholesterolemia, mast cell, nicotine",

author = "Chen Wang and Han Chen and Wei Zhu and Yinchuan Xu and Mingfei Liu and Lianlian Zhu and Fan Yang and Ling Zhang and Xianbao Liu and Zhiwei Zhong and Jing Zhao and Jun Jiang and Meixiang Xiang and Hong Yu and Xinyang Hu and Hong Lu and Jian'an Wang",

note = "Funding Information: This work was supported by the National Basic Research Program of China (973 Program, 2014CB965103), the National High-tech R&D 863 Program (no. 2013AA020101 for X. Hu, no. 2015AA020922 for X. Liu), grants from National Natural Science Foundation of China (no. 81320108003 and 31371498 for J. Wang, no. 81370247 for X. Hu, no. 81570233 for X. Liu, no. 81500334 for H. Chen, no. 81470384 and 81270179 for M. Xiang, no. 81573641 for L. Zhang, no. 81100141 for J. Jiang), the Qianjiang Talents Project of Science and Technology Department of Zhejiang Province (no. 2013R10032 for H. Chen and no. LY16H280003 for L. Zhang), the Natural Science Foundation of Zhejiang Province (no. LQ16H020004 for H. Chen), and the Fundamental Research Funds for the Central Universities (no. 2016XZZX002-03 for X. Hu). Publisher Copyright: {\textcopyright} 2016 American Heart Association, Inc.",

year = "2017",

month = jan,

day = "1",

doi = "10.1161/ATVBAHA.116.307264",

language = "English",

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pages = "53--65",

number = "1",

}

Wang, C, Chen, H, Zhu, W, Xu, Y, Liu, M, Zhu, L, Yang, F, Zhang, L, Liu, X, Zhong, Z, Zhao, J, Jiang, J, Xiang, M, Yu, H, Hu, X, Lu, H & Wang, J 2017, 'Nicotine accelerates atherosclerosis in Apolipoprotein E-deficient mice by activating α7 nicotinic acetylcholine receptor on mast cells', Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 37, no. 1, pp. 53-65. https://doi.org/10.1161/ATVBAHA.116.307264

TY - JOUR

T1 - Nicotine accelerates atherosclerosis in Apolipoprotein E-deficient mice by activating α7 nicotinic acetylcholine receptor on mast cells

AU - Wang, Chen

AU - Chen, Han

AU - Zhu, Wei

AU - Xu, Yinchuan

AU - Liu, Mingfei

AU - Zhu, Lianlian

AU - Yang, Fan

AU - Zhang, Ling

AU - Liu, Xianbao

AU - Zhong, Zhiwei

AU - Zhao, Jing

AU - Jiang, Jun

AU - Xiang, Meixiang

AU - Yu, Hong

AU - Hu, Xinyang

AU - Lu, Hong

AU - Wang, Jian'an

N1 - Funding Information: This work was supported by the National Basic Research Program of China (973 Program, 2014CB965103), the National High-tech R&D 863 Program (no. 2013AA020101 for X. Hu, no. 2015AA020922 for X. Liu), grants from National Natural Science Foundation of China (no. 81320108003 and 31371498 for J. Wang, no. 81370247 for X. Hu, no. 81570233 for X. Liu, no. 81500334 for H. Chen, no. 81470384 and 81270179 for M. Xiang, no. 81573641 for L. Zhang, no. 81100141 for J. Jiang), the Qianjiang Talents Project of Science and Technology Department of Zhejiang Province (no. 2013R10032 for H. Chen and no. LY16H280003 for L. Zhang), the Natural Science Foundation of Zhejiang Province (no. LQ16H020004 for H. Chen), and the Fundamental Research Funds for the Central Universities (no. 2016XZZX002-03 for X. Hu). Publisher Copyright: © 2016 American Heart Association, Inc.

PY - 2017/1/1

Y1 - 2017/1/1

N2 - 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 α7 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 -/- α7nAChR -/- animals. Conclusions - Activation of α7 nicotinic acetylcholine receptor on MCs is a mechanism by which nicotine enhances atherosclerosis.

AB - 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 α7 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 -/- α7nAChR -/- animals. Conclusions - Activation of α7 nicotinic acetylcholine receptor on MCs is a mechanism by which nicotine enhances atherosclerosis.

KW - apolipoprotein E

KW - atherosclerosis

KW - hypercholesterolemia

KW - mast cell

KW - nicotine

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Nicotine accelerates atherosclerosis in Apolipoprotein E-deficient mice by activating α7 nicotinic acetylcholine receptor on mast cells

Abstract

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Keywords

ASJC Scopus subject areas

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