Nicotine Accelerates Atherosclerosis in Apolipoprotein E-Deficient Mice by Activating α7 Nicotinic Acetylcholine Receptor on Mast Cells

被引：50

作者：

Wang, Chen ^{[1
,2
]}

Chen, Han ^{[1
,2
]}

Zhu, Wei ^{[1
,2
]}

Xu, Yinchuan ^{[1
,2
]}

Liu, Mingfei ^{[2
]}

Zhu, Lianlian ^{[1
,2
]}

Yang, Fan ^{[2
]}

Zhang, Ling ^{[1
,2
]}

Liu, Xianbao ^{[1
,2
]}

Zhong, Zhiwei ^{[1
,2
]}

Zhao, Jing ^{[1
,2
]}

Jiang, Jun ^{[1
,2
]}

Xiang, Meixiang ^{[1
,2
]}

Yu, Hong ^{[1
,2
]}

Hu, Xinyang ^{[1
,2
]}

Lu, Hong ^{[3
]}

Wang, Jian'an ^{[1
,2
]}

机构：

[1] Zhejiang Univ, Affiliated Hosp 2, Dept Cardiol, Coll Med, Hangzhou, Zhejiang, Peoples R China

[2] Cardiovasc Key Lab Zhejiang Prov, Hangzhou, Zhejiang, Peoples R China

[3] Univ Kentucky, Dept Physiol, Saha Cardiovasc Res Ctr, Lexington, KY 40506 USA

来源：

ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY | 2017年 / 37卷 / 01期

基金：

中国国家自然科学基金;

关键词：

apolipoprotein E; atherosclerosis; hypercholesterolemia; mast cell; nicotine; REVERSE CHOLESTEROL TRANSPORT; SMOOTH-MUSCLE-CELLS; PROINFLAMMATORY CYTOKINES; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; SIGNALING PATHWAYS; CHOLINERGIC SYSTEM; AORTIC-ANEURYSMS; PASSIVE SMOKING; HEART-DISEASE;

D O I：

10.1161/ATVBAHA.116.307264

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页码：53 / +

页数：34

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