期刊
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
卷 37, 期 1, 页码 53-+出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/ATVBAHA.116.307264
关键词
apolipoprotein E; atherosclerosis; hypercholesterolemia; mast cell; nicotine
资金
- National Basic Research Program of China (973 Program) [2014CB965103]
- National High-tech RD 863 Program [2013AA020101, 2015AA020922]
- National Natural Science Foundation of China [81320108003, 31371498, 81370247, 81570233, 81500334, 81470384, 81270179, 81573641, 81100141]
- Qianjiang Talents Project of Science and Technology Department of Zhejiang Province [2013R10032, LY16H280003]
- Natural Science Foundation of Zhejiang Province [LQ16H020004]
- Fundamental Research Funds for the Central Universities [2016XZZX002-03]
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.
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