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      Cardiovascular, carcinogenic and reproductive effects of nicotine exposure: A narrative review of the scientific literature

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          Abstract

          The emergence of new tobacco heating products and electronic nicotine delivery systems (ENDS) is changing the way humans are exposed to nicotine. The purpose of this narrative review is to provide a broad overview of published scientific literature with respect to the effects of nicotine on three key health-related areas: 1) cardiovascular risk, 2) carcinogenesis and 3) reproductive outcomes. These areas are known to be particularly vulnerable to the effects of cigarette smoke, and in addition, nicotine has been hypothesized to play a role in disease pathogenesis. Acute toxicity will also be discussed.

          The literature to February 2019 suggests that there is no increased cardiovascular risk of nicotine exposure in consumers who have no underlying cardiovascular pathology. There is scientific consensus that nicotine is not a direct or complete carcinogen, however, it remains to be established whether it plays some role in human cancer propagation and metastasis. These cancer progression pathways have been proposed in models in vitro and in transgenic rodent lines in vivo but have not been demonstrated in cases of human cancer.

          Further studies are needed to determine whether nicotine is linked to decreased fertility in humans. The results from animal studies indicate that nicotine has the potential to act across many mechanisms during fetal development. More studies are needed to address questions regarding nicotine exposure in humans, and this may lead to additional guidance concerning new ENDS entering the market.

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          Most cited references163

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          Causation and causal inference in epidemiology.

          Concepts of cause and causal inference are largely self-taught from early learning experiences. A model of causation that describes causes in terms of sufficient causes and their component causes illuminates important principles such as multi-causality, the dependence of the strength of component causes on the prevalence of complementary component causes, and interaction between component causes. Philosophers agree that causal propositions cannot be proved, and find flaws or practical limitations in all philosophies of causal inference. Hence, the role of logic, belief, and observation in evaluating causal propositions is not settled. Causal inference in epidemiology is better viewed as an exercise in measurement of an effect rather than as a criterion-guided process for deciding whether an effect is present or not.
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            Nicotine stimulates angiogenesis and promotes tumor growth and atherosclerosis.

            We provide anatomic and functional evidence that nicotine induces angiogenesis. We also show that nicotine accelerates the growth of tumor and atheroma in association with increased neovascularization. Nicotine increased endothelial-cell growth and tube formation in vitro, and accelerated fibrovascular growth in vivo. In a mouse model of hind-limb ischemia, nicotine increased capillary and collateral growth, and enhanced tissue perfusion. In mouse models of lung cancer and atherosclerosis, we found that nicotine enhanced lesion growth in association with an increase in lesion vascularity. These effects of nicotine were mediated through nicotinic acetylcholine receptors at nicotine concentrations that are pathophysiologically relevant. The endothelial production of nitric oxide, prostacyclin and vascular endothelial growth factor might have a role in these effects.
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              Acute Impact of Tobacco vs Electronic Cigarette Smoking on Oxidative Stress and Vascular Function.

              The vascular safety of electronic cigarettes (e-Cigarettes) must still be clarified. We compared the impact of e-Cigarettes vs traditional tobacco cigarettes on oxidative stress and endothelial function in healthy smokers and nonsmoker adults.
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                Author and article information

                Contributors
                Role: InvestigationRole: Writing – Original Draft PreparationRole: Writing – Review & Editing
                Role: ConceptualizationRole: SupervisionRole: Writing – Review & Editing
                Journal
                F1000Res
                F1000Res
                F1000Research
                F1000Research
                F1000 Research Limited (London, UK )
                2046-1402
                9 January 2020
                2019
                : 8
                : 1586
                Affiliations
                [1 ]Scientific and Regulatory Affairs, Japan Tobacco International, Genève, Genève, 1202, Switzerland
                [1 ]Obstetrics and Gynecology, McMaster University, Hamilton, Canada
                [1 ]Department of Pharmacology and Toxicology Institute of Pharmaceutical Sciences, Karl-Franzens-University Graz, Graz, Austria
                [1 ]Department of Pharmacology and Toxicology Institute of Pharmaceutical Sciences, Karl-Franzens-University Graz, Graz, Austria
                Japan Tobacco International, Switzerland
                [1 ]Division of Internal Medicine, Department of Clinical Sciences, Danderyd University Hospital, Karolinska Institutet, Stockholm, Sweden
                Japan Tobacco International, Switzerland
                Japan Tobacco International, Switzerland
                Author notes

                Competing interests: The authors of this scientific review are employees of Japan Tobacco International. The views and conclusions contained herein are solely those of the authors and do not necessarily represent the views and conclusions of Japan Tobacco International.

                Competing interests: No competing interests were disclosed.

                Competing interests: No competing interests were disclosed.

                Competing interests: No competing interests were disclosed.

                Competing interests: The authors of this scientific review are employees of Japan Tobacco International. The views and conclusions contained herein are solely those of the authors and do not necessarily represent the views and conclusions of Japan Tobacco International.

                Competing interests: No competing interests were disclosed.

                Competing interests: No competing interests were disclosed.

                Competing interests: The authors of this scientific review are employees of Japan Tobacco International. The views and conclusions contained herein are solely those of the authors and do not necessarily represent the views and conclusions of Japan Tobacco International.

                Author information
                https://orcid.org/0000-0002-8547-3549
                https://orcid.org/0000-0002-9668-8457
                Article
                10.12688/f1000research.20062.2
                7308884
                32595938
                85e778a8-12d5-4800-b40c-76e60417772c
                Copyright: © 2020 Price LR and Martinez J

                This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 20 December 2019
                Funding
                Funded by: Japan Tobacco International
                This project was funded by Japan Tobacco International.
                Categories
                Review
                Articles

                nicotine; electronic nicotine delivery systems,cardiovascular diseases,carcinogenesis,fetal development,fertility,acute toxicity,nicotine replacement therapy

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