Nicotine Accelerates Atherosclerosis in Apolipoprotein E–Deficient Mice by Activating α7 Nicotinic Acetylcholine Receptor on Mast Cells

Wang, Chen; Chen, Han; Zhu, Wei; Xu, Yinchuan; Liu, Mingfei; Zhu, Long‐Guan; Yang, Fan; Zhang, Ling; Liu, Xianbao; Zhong, Zhiwei; Zhao, Jing; Jiang, Jun; Xiang, Meixiang; Yu, Hong; Hu, Xinyang; Lü, Hong; Wang, Jianan

doi:10.1161/atvbaha.116.307264

Cited by 59 publications

(39 citation statements)

References 42 publications

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Section: Discussionmentioning

confidence: 99%

“…CAP is an endogenous neurofeedback regulation, studies have shown that cholinergic agonists acting on α7nAChR-knockout macrophages can not produce the desired anti-inflammatory effect, suggesting that α7nAchR is the necessary receptor for CAP ( 14 ). Under the stimuli of infection, injury or embolism, vagus nerve is activated, a large number of Ach release into peripheral tissue and bind with macrophages, microglia and other antibody on the surface of immune cells ( 14 , 15 ). Activation of α7nAchR, cholinergic anti-inflammatory signal can inhibit the release of IL-1β, IL-6, TNF-α and other inflammatory cytokines and endotoxin through the various signal transduction pathways in the cells, increase the formation of anti-inflammatory factors, thus producing a rapid and efficient regulation of inflammatory response ( 16 , 17 ).…”

Section: Discussionmentioning

confidence: 99%

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α7 nicotinic acetylcholine receptor agonist inhibits the damage of rat hippocampal neurons by TLR4/Myd88/NF-κB signaling pathway during cardiopulmonary bypass

Chen

Sun

Diao

et al. 2017

Molecular Medicine Reports

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The present study aimed to investigate the effect of α7 nicotinic acetylcholine receptor (α7nAChR) agonist on the damage of hippocampal neurons and the expression of toll like receptor 4 (TLR4)/myeloid differentiation primary response 88 (Myd88)/nuclear factor (NF)-κB signal pathway-associated factors in cardiopulmonary bypass (CPB). Sprague Dawley rats were randomly divided into five groups: Sham operation (Sham); CPB; CPB + α7nAChR agonist PHA568487 (PHA); CPB + α7nAChR inhibitor MLA (MLA); and CPB + PHA568487 + TLR4 antagonist (CPT). Blood and brain tissue samples were harvested at 12 h following the withdrawal of CPB. Levels of serum inflammatory factors [interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α] and brain injury markers [S-100β and neuron-specific enolase (NSE)] were measured using ELISA. In addition, pathological histology and apoptosis changes were observed using hematoxylin and eosin staining, and Tunnel assays. Quantitative polymerase chain reaction and western blot assays were used to determine the expression of TLR4, Myd88 and NF-κB mRNA, and protein in the hippocampus. The morphology of hippocampal pyramidal cells in the Sham group was observed to be normal. Pyramidal cells in the CPB, MLA and CPT groups were loosely arranged, and the baselines had disappeared, with clear nucleus pyknosis and neuronal apoptosis. Furthermore, the cells in the PHA group were slightly damaged. IL-1β, IL-6, TNF-α, S-100β and NSE expression levels in the CPB, MLA, and CPT groups were significantly higher compared with that in the Sham group (P<0.05). Compared with CPB group, the expression of inflammatory cytokines in the PHA group was significantly lower (P<0.05). The expression of TLR4, Myd88 and NF-κB mRNA, and protein in the hippocampus of CPB, MLA and CPT groups were significantly higher compared with that in the Sham group, and the PHA group expression was significantly lower compared with the CPB group (P<0.05). α7nAChRs agonist can inhibit the apoptosis of rat brain neurons induced by CPB, and may protect against brain injury through the TLR4/Myd88/NF-κB signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

α7 nicotinic acetylcholine receptor agonist inhibits the damage of rat hippocampal neurons by TLR4/Myd88/NF-κB signaling pathway during cardiopulmonary bypass

Chen

Sun

Diao

et al. 2017

Molecular Medicine Reports

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“…Another study examined the role that mast cells (MCs) have in nicotine-accelerated atherosclerosis. The results indicated that nicotine acts through α7 nAChRs on MCs to exacerbate atherosclerosis by enhancing lesion development; a process that can be blunted by knocking the cells out in vivo [253].…”

Section: Additional Nicotine Studiesmentioning

confidence: 99%

“…Stolle et al [256] demonstrated that cigarette smoke exacerbated Ang II-induced AAA formation, which was associated with an increased expression of MMP-2, -3, -8, -9, and -12. Wang et al [253] showed that nicotine also exacerbated Ang II-induced AAA formation in ApoE −/− , but not in ApoE −/− AMPK-α2 −/− double knockout. In VSMCs in culture, nicotine and Ang II activated AMPK-α2, leading to MMP-2 expression.…”

Section: Additional Nicotine Studiesmentioning

confidence: 99%

Nicotine in Senescence and Atherosclerosis

Centner

Bhide²,

Salazar

2020

Cells

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Cigarette smoke is a known exacerbator of age-related pathologies, such as cardiovascular disease (CVD), atherosclerosis, and cellular aging (senescence). However, the role of nicotine and its major metabolite cotinine is yet to be elucidated. Considering the growing amount of nicotine-containing aerosol use in recent years, the role of nicotine is a relevant public health concern. A number of recent studies and health education sites have focused on nicotine aerosol-induced adverse lung function, and neglected cardiovascular (CV) impairments and diseases. A critical review of the present scientific literature leads to the hypothesis that nicotine mediates the effects of cigarette smoke in the CV system by increasing MAPK signaling, inflammation, and oxidative stress through NADPH oxidase 1 (Nox1), to induce vascular smooth muscle cell (VSMC) senescence. The accumulation of senescent VSMCs in the lesion cap is detrimental as it increases the pathogenesis of atherosclerosis by promoting an unstable plaque phenotype. Therefore, nicotine, and most likely its metabolite cotinine, adversely influence atherosclerosis.

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“…First, pulmonary neuroendocrine and mast cells and neuroepithelial bodies are major sources of 5-HT in BALF (19)(20)(21). Second, the activation of nicotinic acetylcholine receptors in these cells promotes 5-HT synthesis and release (19,(21)(22)(23)(24). Importantly, the concentration of nicotine in the milk of mothers who smoke is 3-fold higher than that in the plasma (25), so PNE pups are consistently exposed to a high concentration of nicotine.…”

mentioning

confidence: 99%

Prolongation of bronchopulmonary C‐fiber–mediated apnea by prenatal nicotinic exposure in rat pups: role of 5‐HT₃receptors

et al. 2019

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Prenatal nicotinic exposure (PNE) reportedly sensitizes bronchopulmonary C‐fibers (PCFs) and prolongs PCF‐mediated apnea in rat pups, contributing to the pathogenesis of sudden infant death syndrome. Serotonin, or 5‐hydroxytryptamine (5‐HT), induces apnea via acting on 5‐HT receptor 3 (5‐HT3R) in PCFs, and among the 5‐HT3R subunits, 5‐HT3B is responsible for shortening the decay time of 5‐HT3R—mediated currents. We examined whether PNE would promote pulmonary 5‐HT secretion and prolong the apnea mediated by 5‐HT3Rs in PCFs via affecting the 5‐HT3B subunit. To this end, the following variables were compared between the control and PNE rat pups: 1) the 5‐HT content in bronchoalveolar lavage fluid, 2) the apneic response to the right atrial bolus injection of phenylbiguanide (a 5‐HT3R agonist) before and after PCF inactivation, 3) 5‐HT3R currents and the stimulus threshold of the action currents of vagal pulmonary C‐neurons, and 4) the immunoreactivity (IR) and mRNA expression of 5‐HT3A and 5‐HT3B in these neurons. Our results showed that PNE up‐regulated the pulmonary 5‐HT concentration and strengthened the PCF 5‐HT3R‐mediated apnea. PNE significantly facilitated neural excitability by shortening the decay time of 5‐HT3R currents, lowering the stimulus threshold, and increasing 5‐HT3B IR. In summary, PNE prolongs the apnea mediated by 5‐HT3Rs in PCFs, likely by increasing 5‐HT3B subunits to enhance the excitability of 5‐HT3 channels.—Zhao, L., Gao, X., Zhuang, J., Wallen, M., Leng, S., Xu, F. Prolongation of bronchopulmonary C‐fiber—mediated apnea by prenatal nicotinic exposure in rat pups: role of 5‐HT3 receptors. FASEB J. 33, 10731–10741 (2019). http://www.fasebj.org

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Nicotine Accelerates Atherosclerosis in Apolipoprotein E–Deficient Mice by Activating α7 Nicotinic Acetylcholine Receptor on Mast Cells

Abstract: Activation of α7 nicotinic acetylcholine receptor on MCs is a mechanism by which nicotine enhances atherosclerosis.

Cited by 59 publications

References 42 publications

α7 nicotinic acetylcholine receptor agonist inhibits the damage of rat hippocampal neurons by TLR4/Myd88/NF-κB signaling pathway during cardiopulmonary bypass

α7 nicotinic acetylcholine receptor agonist inhibits the damage of rat hippocampal neurons by TLR4/Myd88/NF-κB signaling pathway during cardiopulmonary bypass

Nicotine in Senescence and Atherosclerosis

Prolongation of bronchopulmonary C‐fiber–mediated apnea by prenatal nicotinic exposure in rat pups: role of 5‐HT₃receptors

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Nicotine Accelerates Atherosclerosis in Apolipoprotein E–Deficient Mice by Activating α7 Nicotinic Acetylcholine Receptor on Mast Cells

Abstract: Activation of α7 nicotinic acetylcholine receptor on MCs is a mechanism by which nicotine enhances atherosclerosis.

Cited by 59 publications

References 42 publications

α7 nicotinic acetylcholine receptor agonist inhibits the damage of rat hippocampal neurons by TLR4/Myd88/NF-κB signaling pathway during cardiopulmonary bypass

α7 nicotinic acetylcholine receptor agonist inhibits the damage of rat hippocampal neurons by TLR4/Myd88/NF-κB signaling pathway during cardiopulmonary bypass

Nicotine in Senescence and Atherosclerosis

Prolongation of bronchopulmonary C‐fiber–mediated apnea by prenatal nicotinic exposure in rat pups: role of 5‐HT3receptors

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Prolongation of bronchopulmonary C‐fiber–mediated apnea by prenatal nicotinic exposure in rat pups: role of 5‐HT₃receptors