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 - 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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U2 - 10.1161/ATVBAHA.116.307264
DO - 10.1161/ATVBAHA.116.307264
M3 - Article
C2 - 27834689
AN - SCOPUS:84995444899
SN - 1079-5642
VL - 37
SP - 53
EP - 65
JO - Arteriosclerosis, Thrombosis, and Vascular Biology
JF - Arteriosclerosis, Thrombosis, and Vascular Biology
IS - 1
ER -