Modeling Cardiovascular Risks of E-Cigarettes With Human-Induced Pluripotent Stem Cell-Derived Endothelial Cells
AuthorLee, Won Hee
Bae, Hye Ryeong
Nadeau, Kari C
Springer, Matthew L
Schick, Suzaynn F
Wu, Joseph C
AffiliationUniv Arizona, Coll Med, Dept Basic Med Sci
MetadataShow full item record
PublisherELSEVIER SCIENCE INC
CitationLee, W. H., Ong, S. G., Zhou, Y., Tian, L., Bae, H. R., Baker, N., ... & Springer, M. L. (2019). Modeling Cardiovascular Risks of E-Cigarettes With Human-Induced Pluripotent Stem Cell–Derived Endothelial Cells. Journal of the American College of Cardiology, 73(21), 2722-2737.
Rights© 2019 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION, PUBLISHED BY ELSEVIER.
Collection InformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at firstname.lastname@example.org.
AbstractBACKGROUND Electronic cigarettes (e-cigarettes) have experienced a tremendous increase in use. Unlike cigarette smoking, the effects of e-cigarettes and their constituents on mediating vascular health remain understudied. However, given their increasing popularity, it is imperative to evaluate the health risks of e-cigarettes, including the effects of their ingredients, especially nicotine and flavorings. OBJECTIVES The purpose of this study was to investigate the effects of flavored e-cigarette liquids (e-liquids) and serum isolated from e-cigarette users on endothelial health and endothelial cell-dependent macrophage activation. METHODS Human-induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) and a high-throughput screening approach were used to assess endothelial integrity following exposure to 6 different e-liquids with varying nicotine concentrations and to serum from e-cigarette users. RESULTS The cytotoxicity of the e-liquids varied considerably, with the cinnamon-flavored product being most potent and leading to significantly decreased cell viability, increased reactive oxygen species (ROS) levels, caspase 3/7 activity, and low-density lipoprotein uptake, activation of oxidative stress-related pathway, and impaired tube formation and migration, confirming endothelial dysfunction. Upon exposure of ECs to e-liquid, conditioned media induced macrophage polarization into a pro-inflammatory state, eliciting the production of interleukin-1 beta and -6, leading to increased ROS. After exposure of human iPSC-ECs to serum of e-cigarette users, increased ROS linked to endothelial dysfunction was observed, as indicated by impaired pro-angiogenic properties. There was also an observed increase in inflammatory cytokine expression in the serum of e-cigarette users. CONCLUSIONS Acute exposure to flavored e-liquids or e-cigarette use exacerbates endothelial dysfunction, which often precedes cardiovascular diseases. (C) 2019 by the American College of Cardiology Foundation.
NoteFinal accepted manuscript; available online 27 May 2019.
VersionFinal accepted manuscript
SponsorsAmerican Heart Association (AHA) Scientist Development Grant [16SDG27560003]; Stanford Diabetes Research Center - National Institutes of Health (NIH) [P30DK116074]; NIH [R00 HL130416, R01 HL141371, P50-CA-180890-01, R01 HL120062, U54HL120163]; University of California Tobacco Related Disease Research Program [27IR-0012, 24RT-0039]; AHA [17MERIT33610009]; U.S. Food and Drug Administration Center for Tobacco Products
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