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.
|Number of pages||13|
|Journal||Arteriosclerosis, Thrombosis, and Vascular Biology|
|State||Published - Jan 1 2017|
Bibliographical noteFunding 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).
© 2016 American Heart Association, Inc.
- apolipoprotein E
- mast cell
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine