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      Chronic snus use in healthy males alters endothelial function and increases arterial stiffness

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          Abstract

          Background

          Snus usage is commonly touted as a safer alternative to cigarette smoking. However, recent studies have demonstrated possible adverse cardiovascular effects in chronic snus users. The present study evaluates the effects of chronic snus use on vascular function by assessing central arterial stiffness and endothelial vasodilatory function in healthy chronic snus users as compared to matched non-users.

          Methods and results

          Fifty healthy males (24 snus users, 26 age-matched controls) with a mean age of 44 years were included in the study. Arterial stiffness was assessed employing both pulse wave velocity and pulse wave analysis. Endothelial vasodilatory function was measured by venous occlusion plethysmography, utilizing intra-arterial administration of acetylcholine, glyceryl trinitrate and bradykinin to further gauge endothelium-dependent and -independent vasodilatory function. Arterial stiffness was significantly higher in chronic snus users as compared to controls: pulse wave velocity [m/s]: 6.6±0.8 vs 7.1±0.9 resp. ( p = 0.026), augmentation index corrected for heart rate [%]: 0.1±13.2 vs 7.3±7.8 resp. ( p = 0.023). Endothelial independent vasodilation, i.e. the reaction to glyceryl trinitrate, was significantly lower in snus users as measured by venous occlusion plethysmography.

          Conclusions

          The results of this study show an increased arterial stiffness and an underlying endothelial dysfunction in daily snus users as compared to matched non-tobacco controls. These findings indicate that long-term use of snus may alter the function of the endothelium and therefore reinforces the assertion that chronic snus use is correlated to an increased risk of development of cardiovascular disease.

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          Most cited references42

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          G*Power 3: A flexible statistical power analysis program for the social, behavioral, and biomedical sciences

          G*Power (Erdfelder, Faul, & Buchner, 1996) was designed as a general stand-alone power analysis program for statistical tests commonly used in social and behavioral research. G*Power 3 is a major extension of, and improvement over, the previous versions. It runs on widely used computer platforms (i.e., Windows XP, Windows Vista, and Mac OS X 10.4) and covers many different statistical tests of the t, F, and chi2 test families. In addition, it includes power analyses for z tests and some exact tests. G*Power 3 provides improved effect size calculators and graphic options, supports both distribution-based and design-based input modes, and offers all types of power analyses in which users might be interested. Like its predecessors, G*Power 3 is free.
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            Reactive oxygen species in inflammation and tissue injury.

            Abstract Reactive oxygen species (ROS) are key signaling molecules that play an important role in the progression of inflammatory disorders. An enhanced ROS generation by polymorphonuclear neutrophils (PMNs) at the site of inflammation causes endothelial dysfunction and tissue injury. The vascular endothelium plays an important role in passage of macromolecules and inflammatory cells from the blood to tissue. Under the inflammatory conditions, oxidative stress produced by PMNs leads to the opening of inter-endothelial junctions and promotes the migration of inflammatory cells across the endothelial barrier. The migrated inflammatory cells not only help in the clearance of pathogens and foreign particles but also lead to tissue injury. The current review compiles the past and current research in the area of inflammation with particular emphasis on oxidative stress-mediated signaling mechanisms that are involved in inflammation and tissue injury.
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              Endothelial Cell Dysfunction and the Pathobiology of Atherosclerosis.

              Dysfunction of the endothelial lining of lesion-prone areas of the arterial vasculature is an important contributor to the pathobiology of atherosclerotic cardiovascular disease. Endothelial cell dysfunction, in its broadest sense, encompasses a constellation of various nonadaptive alterations in functional phenotype, which have important implications for the regulation of hemostasis and thrombosis, local vascular tone and redox balance, and the orchestration of acute and chronic inflammatory reactions within the arterial wall. In this review, we trace the evolution of the concept of endothelial cell dysfunction, focusing on recent insights into the cellular and molecular mechanisms that underlie its pivotal roles in atherosclerotic lesion initiation and progression; explore its relationship to classic, as well as more recently defined, clinical risk factors for atherosclerotic cardiovascular disease; consider current approaches to the clinical assessment of endothelial cell dysfunction; and outline some promising new directions for its early detection and treatment.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Writing – original draftRole: Writing – review & editing
                Role: InvestigationRole: MethodologyRole: Writing – review & editing
                Role: ResourcesRole: Writing – review & editing
                Role: MethodologyRole: SupervisionRole: VisualizationRole: Writing – review & editing
                Role: InvestigationRole: MethodologyRole: Writing – review & editing
                Role: ConceptualizationRole: Project administrationRole: ResourcesRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: Project administrationRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS One
                plos
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                3 June 2022
                2022
                : 17
                : 6
                : e0268746
                Affiliations
                [1 ] Division of Internal Medicine, Department of Clinical Sciences, Karolinska Institutet, Danderyd University Hospital, Stockholm, Sweden
                [2 ] Division of Pulmonology, Department of Medicine II, Medical University of Vienna, Vienna, Austria
                [3 ] Division of Medicine, Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden
                [4 ] Division of Cardiovascular Medicine, Department of Clinical Sciences, Karolinska Institutet, Danderyd University Hospital, Stockholm, Sweden
                Medical University Innsbruck, AUSTRIA
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                https://orcid.org/0000-0001-5969-8165
                https://orcid.org/0000-0002-2574-479X
                https://orcid.org/0000-0003-2380-2607
                Article
                PONE-D-20-38548
                10.1371/journal.pone.0268746
                9165771
                35657943
                d7f79d76-01c6-4eaf-9bae-b8a47322d462
                © 2022 Antoniewicz et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 17 December 2020
                : 6 May 2022
                Page count
                Figures: 2, Tables: 1, Pages: 13
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100003793, Hjärt-Lungfonden;
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100010819, Stiftelsen Tornspiran;
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100006285, Magnus Bergvalls Stiftelse;
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100002960, Västerbotten Läns Landsting;
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100004047, Karolinska Institutet;
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100004348, Stockholms Läns Landsting;
                Award Recipient :
                This work was supported by the Swedish Society of Medicine, the Swedish Heart-lung foundation, the Swedish Heart and Lung Association, the Tornspiran Foundation, Magnus Bergvall foundation and Västerbotten County Council. Dr. Magnus Lundbäck is supported by a clinical post-doctoral support from Karolinska Institutet and Stockholm County Council.
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