Nicotinic acetylcholine receptor signaling in atherogenesis

Santanam, Nalini; Thornhill, Brent A.; Lau, Jamie K.; Crabtree, Clayton M.; Cook, Charles E.; Brown, Kathleen C.; Dasgupta, Piyali

doi:10.1016/j.atherosclerosis.2012.07.041

Cited by 44 publications

(46 citation statements)

References 53 publications

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“…Their results indicated the importance of nAChR; however, they also observed nAChR-independent signaling. nAChRs are pentameric ligand-gated cation channels composed of 5 subunits and are permeable to Na + , K + , and Ca 2+ [5]. The subunit composition of nAChR is important as it affects its Ca 2+ permeability [25] In gingival epithelial cells, the expression of α3, α5, α7, α9, α2, and β4 subunits of this channel have been reported [26-28]; these subunits transduce the nicotine-binding signal [14,16,20,29].…”

Section: Discussionmentioning

confidence: 99%

“…Nicotine also induces proliferation of vascular smooth muscle cells, which is an important contributor to the growth of atherosclerotic plaques. Moreover, nicotine contributes to the progression of plaque formation by angiogenic activity through the nicotinic acetylcholine receptor (nAChR), and can also disturb lipid metabolism [4,5]. All these effects promote the development of pathological processes contributing to atherosclerosis; however, direct evidence for nicotine’s contribution to atherosclerosis is not currently available.…”

Section: Introductionmentioning

confidence: 99%

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Nicotine-Induced Expression of Low-Density Lipoprotein Receptor in Oral Epithelial Cells

et al. 2013

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BackgroundNicotine use is one of the most important risk factors for the development of cardiovascular and periodontal diseases. Numerous reports have suggested the possible contribution of disturbed lipid metabolism for the development of both disease groups. Despite these observations, little is known about the relationship between tobacco smoking and the development of these diseases. Our previous microarray data revealed that nicotine induced low-density lipoprotein receptor (LDLR) expression in oral epithelial cells (OECs). The aim of the present study was to confirm nicotine-mediated LDLR induction and to elucidate the signaling mechanisms leading to the augmented expression of LDLR in OECs.Methods and ResultsLDLR and nicotinic acetylcholine receptor (nAChR) subunit expression was detected by real-time PCR. The production of LDLR was demonstrated by immunofluorescence staining. nAChR-mediated LDLR induction was examined by pre-incubation of the cells with its specific inhibitor, α-bungarotoxin (α-BTX). The functional importance of transcription factor specific protein 1 (Sp1) was examined by luciferase assay, mithramycin pre-incubation or by small interfering RNA (siRNA) transfection. The specific binding of Sp1 to R3 region of LDLR 5’-untranslated region was demonstrated with electrophoretic mobility shift assay (EMSA) and streptavidin-agarose precipitation assay followed by western blotting. The results confirmed that nicotine induced LDLR expression at the transcriptional level. Nicotine was sensed by nAChR and the signal was transduced by Sp1 which bound to the R3 region of LDLR gene. Augmented production of LDLR in the gingival epithelial cells was further demonstrated by immunofluorescence staining using the gingival tissues obtained from the smoking patients. ConclusionsTaken together, the results suggested that nicotine might contribute to the development of both cardiovascular and periodontal diseases by inducing the LDLR in OECs thereby disturbing lipid metabolism.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Nicotine-Induced Expression of Low-Density Lipoprotein Receptor in Oral Epithelial Cells

et al. 2013

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“…The evidence that nicotine might be a risk factor for the development of cardiovascular disease is far less compelling. It has been suggested that nicotine may contribute to atherogenesis directly through activation of nicotinic acetylcholine receptors in the blood vessels [37,38] and indirectly via formation of inflammatory mediators with proatherosclerotic activity [39]. This evidence is drawn from laboratory studies using higher doses and more prolonged exposures than would ever be seen in real life.…”

Section: Effects Of Nicotine Inhalation By the E-cigarette Usermentioning

confidence: 99%

A critique of the US Surgeon General’s conclusions regarding e-cigarette use among youth and young adults in the United States of America

Polosa

Russell²,

Nitzkin³

et al. 2017

Harm Reduct J

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Background: In December 2016, the Surgeon General published a report that concluded e-cigarette use among youth and young adults is becoming a major public health concern in the United States of America. Methods: Re-analysis of key data sources on nicotine toxicity and prevalence of youth use of e-cigarettes cited in the Surgeon General report as the basis for its conclusions. Results: Multiple years of nationally representative surveys indicate the majority of e-cigarette use among US youth is either infrequent or experimental, and negligible among never-smoking youth. The majority of the very small proportion of US youth who use e-cigarettes on a regular basis, consume nicotine-free products. The sharpest declines in US youth smoking rates have occurred as e-cigarettes have become increasingly available. Most of the evidence presented in the Surgeon General's discussion of nicotine harm is not applicable to e-cigarette use, because it relies almost exclusively on exposure to nicotine in the cigarette smoke and not to nicotine present in ecigarette aerosol emissions. Moreover, the referenced literature describes effects in adults, not youth, and in animal models that have little relevance to real-world e-cigarette use by youth. The Surgeon General's report is an excellent reference document for the adverse outcomes due to nicotine in combination with several other toxicants present in tobacco smoke, but fails to address the risks of nicotine decoupled from tobacco smoke constituents. The report exaggerates the toxicity of propylene glycol (PG) and vegetable glycerin (VG) by focusing on experimental conditions that do not reflect use in the real-world and provides little discussion of emerging evidence that e-cigarettes may significantly reduce harm to smokers who have completely switched. Conclusions: The U.S. Surgeon General's claim that e-cigarette use among U.S. youth and young adults is an emerging public health concern does not appear to be supported by the best available evidence on the health risks of nicotine use and population survey data on prevalence of frequent e-cigarette use. Nonetheless, patterns of e-cigarettes use in youth must be constantly monitored for early detection of significant changes. The next US Surgeon General should consider the possibility that future generations of young Americans will be less likely to start smoking tobacco because of, not in spite of, the availability of e-cigarettes.

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“…Free fatty acids are toxic to the endothelium, although it appears that the nicotinic acetylcholine receptor signaling may be more responsible for the atherogenic effect of nicotine. 23 Nicotine affects essentially every organ through neuroeffector, chemosensitive, sympathetic, and parasympathetic activities, blood flow, endothelial cell injury, epinephrine and cortisol release, and lipid effects. Nicotine causes peptic ulcer and gastrointestinal cancers.…”

Section: It Ignores Nicotine and Its Harmful Effectsmentioning

confidence: 99%

Electronic Cigarettes: Vulnerability of Youth

Schraufnagel

2015

Pediatric Allergy, Immunology, and Pulmonology

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Nicotinic acetylcholine receptor signaling in atherogenesis

Cited by 44 publications

References 53 publications

Nicotine-Induced Expression of Low-Density Lipoprotein Receptor in Oral Epithelial Cells

Nicotine-Induced Expression of Low-Density Lipoprotein Receptor in Oral Epithelial Cells

A critique of the US Surgeon General’s conclusions regarding e-cigarette use among youth and young adults in the United States of America

Electronic Cigarettes: Vulnerability of Youth

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