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

Research output: Contribution to journalArticlepeer-review

48 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 languageEnglish
Pages (from-to)53-65
Number of pages13
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume37
Issue number1
DOIs
StatePublished - Jan 1 2017

Bibliographical note

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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