Chen Wang1, Han Chen1, Wei Zhu1, Yinchuan Xu1, Mingfei Liu1, Lianlian Zhu1, Fan Yang1, Ling Zhang1, Xianbao Liu1, Zhiwei Zhong1, Jing Zhao1, Jun Jiang1, Meixiang Xiang1, Hong Yu1, Xinyang Hu1, Hong Lu1, Jian'an Wang2. 1. From the Department of Cardiology, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, PR China (C.W., H.C., W.Z., Y.X., L. Zhu, L. Zhang, X.L., Z.Z., J.Z., J.J., M.X., H.Y., X.H., J.W.); Cardiovascular Key Laboratory of Zhejiang Province, Hangzhou, PR China (C.W., H.C., W.Z., Y.X., M.L., L. Zhu, F.Y., L. Zhang, X.L., Z.Z., J.Z., J.J., M.X., H.Y., X.H., J.W.); and Saha Cardiovascular Research Center, Departments of Physiology, University of Kentucky, Lexington (H.L.). 2. From the Department of Cardiology, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, PR China (C.W., H.C., W.Z., Y.X., L. Zhu, L. Zhang, X.L., Z.Z., J.Z., J.J., M.X., H.Y., X.H., J.W.); Cardiovascular Key Laboratory of Zhejiang Province, Hangzhou, PR China (C.W., H.C., W.Z., Y.X., M.L., L. Zhu, F.Y., L. Zhang, X.L., Z.Z., J.Z., J.J., M.X., H.Y., X.H., J.W.); and Saha Cardiovascular Research Center, Departments of Physiology, University of Kentucky, Lexington (H.L.). wja@zju.edu.cn.
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-/-KitW-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-/-KitW-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.
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-/-KitW-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-/-KitW-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.
Authors: Jorge Espinoza-Derout; Kamrul M Hasan; Xuesi M Shao; Maria C Jordan; Carl Sims; Desean L Lee; Satyesh Sinha; Zena Simmons; Norma Mtume; Yanjun Liu; Kenneth P Roos; Amiya P Sinha-Hikim; Theodore C Friedman Journal: Am J Physiol Heart Circ Physiol Date: 2019-06-07 Impact factor: 4.733
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