(714.5) Effect of Mediators in the Plasma of E-Cigarette Users on Endothelial and Epithelial Cell Metabolism

Poster Board Number: E69

Ramamurthy Chitteti (School of Medicine, University of California San Diego, School of Medicine, University of California San Diego), Juan Hertz (School of Medicine, University of California San Diego, School of Medicine, University of California San Diego), Jorge Masso-Silva (University of California San Diego, University of California San Diego), John Shin (University of California San Diego, University of California San Diego), Laura Alexander (University of California San Diego, University of California San Diego), Hemal Patel (School of Medicine, University of California San Diego, School of Medicine, University of California San Diego), David M. Roth (School of Medicine, University of California San Diego, School of Medicine, University of California San Diego)

Background:  Tobacco smoking is a major risk factor for cardiovascular and lung disease. Inhalation of aerosols formed by electronic nicotine delivery systems (ENDS) such as E-cigarettes (E-cigs) may expose the user to harms beyond those of nicotine alone. Data on the cardiovascular risks of E-cigs and vaping devices remain inconclusive. However, exposure to E-cigs  induces the release of multiple substances, including exosomes and metabolites, into the bloodstream. There is limited information on the role of these exosomes and metabolites on cellular homeostasis. Mitochondria are highly sensitive to cigarette smoke, however E-cig aerosol induced changes in mitochondrial function are not well studied. We investigated the effects of E-cig plasma mediators on metabolism and function in human vascular endothelial (EA.hy 926) and lung epithelial cells (A549). 

Hypothesis: Plasma from E-cig users will induce alterations in the metabolism and mitochondrial function of endothelial and lung epithelial cells.

Methods:  A longitudinal cohort study was conducted on subjects who exclusively used E-cigarettes (n=21) and 10 non-smoking, non-vaping subjects. We included active E-cig use without known lung disease and with normal lung function, between the ages of 18-30 years. E-cig use was confirmed with in-person interviews and plasma cotinine levels. Active E-cig use was defined as use of gt;0.5-1 mL e-liquid/day or 3.5-7 mL/week for gt;6 months. Plasma was isolated and stored at -70°C until exosomes were profiled. The effects of E-cig plasma (1%, 1h conditioning) mediators were assessed in vitro on endothelial cells (8x104/well) and epithelial cells (5x104/well) using the Seahorse XF Cell Mito Stress Test.

Results:  Results were standardized for cell number and FCCP concentrations for both EA.hy 926 and A549 cells. Maximal mitochondrial respiration and spare capacity were decreased in human vascular endothelial cells and epithelial cells treated with E-cig plasma relative to plasma from non-smoker/non-vapers. Basal respiration and ATP-linked respiration was not different after treatment with plasma from E-cig users versus non-smoker/non-vapers in either cell type. 

Conclusions:  To our knowledge, our results are the first to suggest that factors in the plasma of E-cig users lead to reduction in maximal metabolic rates of human endothelial and lung cells in vitro. These results have important implications regarding the effects of E-cig use on cellular metabolism and mitochondrial function and eventual public health recommendations. We are currently investigating the underlying mechanisms of action of E-cig plasma components on mitochondrial biology.

lt;bgt;T31IP1929lt;/bgt; (DM Roth) 07/01/2020 amp;ndash; 06/30/2022
Funding Source: University of California TRDRP 2020 lt;igt;Annual: lt;/igt;$260,000 lt;igt;Entire Period: lt;/igt;$520,000
lt;bgt;Project Title: Exosomes and vascular disease risk in new and emerging tobacco productslt;/bgt;
lt;bgt;1 R21 AG058174-01A1lt;/bgt; (DM Roth) 09/01/2018 amp;ndash; 06/30/2021
Funding Source: NIH/NIA lt;igt;Annual: lt;/igt;$236,188 lt;igt;Entire Period:lt;/igt; $432,438
lt;bgt;Project Title: Exosomes in Aging and Operative Hypothermic Circulatory Arrest.lt;/bgt;