Proponents for electronic cigarettes (E-cigs) claim that they are a safe alternative to tobacco-based cigarettes; however, little is known about the long-term effects of exposure to E-cig vapor on vascular function. The purpose of this study was to determine the cardiovascular consequences of chronic E-cig exposure. Female mice (C57BL/6 background strain) were randomly assigned to chronic daily exposure to E-cig vapor, standard (3R4F reference) cigarette smoke, or filtered air ( n = 15/group). Respective whole body exposures consisted of four 1-h-exposure time blocks, separated by 30-min intervals of fresh air breaks, resulting in intermittent daily exposure for a total of 4 h/day, 5 days/wk for 8 mo. Noninvasive ultrasonography was used to assess cardiac function and aortic arterial stiffness (AS), measured as pulse wave velocity, at three times points (before, during, and after chronic exposure). Upon completion of the 8-mo exposure, ex vivo wire tension myography and force transduction were used to measure changes in thoracic aortic tension in response to vasoactive-inducing compounds. AS increased 2.5- and 2.8-fold in E-cig- and 3R4F-exposed mice, respectively, compared with air-exposed control mice ( P < 0.05). The maximal aortic relaxation to methacholine was 24% and 33% lower in E-cig- and 3R4F-exposed mice, respectively, than in controls ( P < 0.05). No differences were noted in sodium nitroprusside dilation between the groups. 3R4F exposure altered cardiac function by reducing fractional shortening and ejection fraction after 8 mo ( P < 0.05). A similar, although not statistically significant, tendency was also observed with E-cig exposure ( P < 0.10). Histological and respiratory function data support emphysema-associated changes in 3R4F-exposed, but not E-cig-exposed, mice. Chronic exposure to E-cig vapor accelerates AS, significantly impairs aortic endothelial function, and may lead to impaired cardiac function. The clinical implication from this study is that chronic use of E-cigs, even at relatively low exposure levels, induces cardiovascular dysfunction. NEW & NOTEWORTHY Electronic cigarettes (E-cigs) are marketed as safe, but there has been insufficient long-term exposure to humans to justify these claims. This is the first study to report the long-term in vivo vascular consequences of 8 mo of exposure to E-cig vapor in mice (equivalent to ~25 yr of exposure in humans). We report that E-cig exposure increases arterial stiffness and impairs normal vascular reactivity responses, similar to other risk factors, including cigarette smoking, which contribute to the development of cardiovascular disease.
Effects of Chronic Electronic Cigarette Use on Glucose Metabolism Hannah Hoskinson Traditional cigarette usage has been linked to a number of nefarious metabolic effects, including insulin resistance; however, the effects of electronic cigarettes (E-cigs) are not currently known. Advertised as a safe alternative for traditional tobacco cigarettes, E-cigs still contain some of the same harmful chemicals as tobacco cigarettes. Through this study, we hope to gain perspective on whether e-cigs play into the development of altered glucose homeostasis. C57BL/6 mice were divided between E-cig (n=15) and control (n=15) groups and exposed to either cappuccino flavored E-cig vapor or filtered air for 4 h/d, 5 d/wk for 8 months. Fasting blood glucose (FBG) and glucose tolerance were observed after 6 months of exposure. Glucose was administered either orally or IP at 2g glucose/kg body mass. Following an overnight fast, an oral glucose tolerance test (OGTT) was performed prior to E-cig exposure; on a separate day another OGT was performed immediately after a 4-hour exposure period. In addition, an intraperitoneal glucose tolerance test (IPGTT) was performed immediately after a 4-hour exposure period in a subset of mice (N=4). At the conclusion of 8 months of exposure, pancreas tissue was harvested and assessed in a subset of mice (n=6). Total body mass was similar between E-cig and air exposed groups at six months (E-cig: 28.7 ±1.1g vs Control: 28.8 ±1.45g) and eight months (E-cig: 29.5±1.62g vs Control: 28.9±1.06g). FBG prior to E-cig exposure tended to be higher in E-cig vs control mice (p=.13), while glucose following exposure were increased in the E-cig group (143.8±6mg/dL vs. 118.8±8mg/dL, p=0.05). During the IPGTT, E-cig animals presented with a higher peak blood glucose (225±7mg/dL vs. 180±15mg/dL, p=0.03), as well as a higher total area under the curve (AUC) than controls (18228 ± 742 vs 15069 ± 667 respectively, p=0.02). E-cig animals did not have a different β-cell density, insulin positive area, or number of SIRT1(+) nuclei. However, SIRT1 density (determined by number of SIRT1(+) nuclei/islet area) was lower in E-cig mice versus control (E-cig: 2.8E-4 ± 5.0E-5 nuclei/µm vs Controls: 4.4E-4 ± 5.0E-5 nuclei/µm, p=0.05). Total SIRT1 (E-cig: 1449 ± 301ng vs Control: 1297 ± 251ng) and UCP2 (E-cig: 0.08 ± 0.009 vs. Control: 0.10 ± 0.01, AU) protein in the pancreas was not different between groups. In conclusion, chronic exposure to E-cig vapor resulted in modestly higher resting and stimulated blood glucose. Although total pancreatic SIRT1 protein levels were not affected, the density of SIRT1 positive β-cells was reduced in E-cig animals. Future research needs to determine if other pancreatic proteins and mechanisms are negatively affected because of E-cig exposure. iii ABBREVIATIONS E-cig Electronic cigarette T2DM Type 2 Diabetes Mellitus UCP Uncoupling protein GLUT4 Glucose transporter 4 PI3K Phosphoinositide 3-kinase DHEA Dehydroepiandrosterone ACTH Adrenocorticotropic hormone HbA1C Hemoglobin a1C HDL High density ...
BackgroundElectronic cigarettes (E‐cigs) have exponentially increased in popularity and usage due to the perception that e‐cigs are safe, their usefulness as a cigarette‐smoking cessation tool, and the appeal of heavily marketed flavors. There is little known about the long‐term effects of E‐cig vapor exposure, particularly in the context of vascular dysfunction. We hypothesize that the long‐term use of E‐cig vapor decreased aortic function, and increase aortic stiffness.MethodsData were obtained from C57BL/6 female mice exposed to 3R4F reference cigarette (N=5–7), cappuccino flavored E‐vapor (18 mg/ml nicotine, N=7), or filtered air (N=7–8) for 4 h/day, 5 d/wk for 8 months. Food and water were administered ad libitum. Before and after the exposure, in‐vivo aortic stiffness (pulse wave velocity) was measured using B‐mode and Doppler ultrasound by obtain blood flow signals at the aortic arch and before the carotid bifurcation from a single image, which were gated to the EKG. At the end of the exposure the thoracic aorta was dissected, sectioned into rings and mounted onto an ex‐vivo wire tension myograph system. Force transduction was used to measure the changes in aortic tension in response to methacholine, or sodium nitroprusside.ResultsAortic stiffness increased (0.45±0.20 m/s) in the air‐exposed group, reflecting the normal aging process. However, an accelerated age‐associated aortic stiffness was noted in the cigarette (1.28±0.27 m/s) and E‐cig (1.14±0.24 m/s) groups (ANOVA, p<0.05). In animals exposed to filtered air, the maximal aortic relaxation achieved to methacholine was 90%, compared to 60% and 70% in the cigarette and E‐cig groups, respectively (p<0.05). No differences were noted in sodium nitroprusside dilation between groups.ConclusionOur data suggests that 8 months of E‐cig significantly accelerated the age‐associated increase in aortic stiffness, and significantly impaired aortic endothelial‐dependent but not endothelial‐independent dilation. These data show the E‐cigs induce similar vascular dysfunction to cigarette smoke exposure suggesting that E‐cig have similar risk to develop accelerated cardiovascular aging and disease.Support or Funding InformationNational Institutes of Health Grant: 1P20 GM‐109098West Virginia University – Marshall University Collaborative Health Research Grants
IntroductionElectronic cigarettes (E‐cigs) are gaining popularity in the United States and worldwide. Little is currently known about the effects of chronic E‐cigarette exposure on cytokine expression throughout the body.MethodsC57BL/6 female mice were randomly assigned to cappuccino flavored E‐vapor (18 mg/ml nicotine, N=12) or filtered air (N=13) exposed groups. Animals were exposed 4 hours per day, 5 days per week for 8 months. After exposure major organs including lung, serum, and gastrocnemius were removed and flash frozen for cytokine analysis. Lung and skeletal muscle (i.e. gastrocnemius muscle) were homogenized with Tris‐HCL‐ buffer. Total protein from homogenates and serum were analyzed with the Bradford method and equal concentrations of total protein were analyzed using a Meso Scale Discovery U‐Plex kit according to manufacturer's instructions. Cytokines analyzed included: vascular endothelial growth factor (VEGF), Interleukin (IL)‐6, IL‐5, IL‐4, tumor necrosis factor‐ alpha (TNF‐α), IL‐1β, IL‐15, IL‐ 10, interferon gamma (IFN‐γ) and granulocyte‐macrophage colony‐stimulating factor (GM‐CSF).ResultsThe lungs of E‐cig exposed mice had 54% less VEGF compared to air exposed controls. IL‐6 was reduced by 57% in serum, but IL‐6 increased 994% in the skeletal muscle of E‐cig exposed mice compared to air exposed controls. IL‐10 was reduced by 87% in the gastrocnemius muscle of E‐cig exposed mice compared to air exposed control mice. No significant differences in the remaining factors (i.e. IL‐5, IL‐4, TNF‐α, IL‐1β, IL‐15, IFNγ, GM‐CSF) were identified between E‐cig and air groups in any of the other organs/tissues tested.DiscussionThe results of this study have implications for immune system response time and muscle growth/regeneration. IL‐6 is important for initiating immune system responses, decreases in its expression may lead to increased frequency or duration of infections by viruses or bacteria. IL‐10 in muscle has been shown to influence macrophages to increase anabolic capability of the muscle. Decreases in VEGF may indicate altered angiogenic potential, changes in muscle permeability and/or increased potential of apoptosis in the lung. Long‐term exposure to E‐cig vapor results in changes in cytokines and growth factors that may negatively influence immune and angiogenic potential.Support or Funding InformationNIH P20GM103434 (West Virginia IDeA Network for Biomedical Research Excellence) and Marshall‐WVU Health Cooperative AwardThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
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