Exposure to Flavored E-Cigarette Liquids, E-Cigarette Use Exacerbates Cell Dysfunction

Acute exposure to flavored e-liquids or e-cigarette use may exacerbate endothelial cell dysfunction, according to research published May 27 in the Journal of the American College of Cardiology.

Won Hee Lee, PhD, et al., used induced pluripotent stem cells-derived endothelial cells (iPSC-ECs) from three healthy individuals and a subject population consisting of five healthy non-smokers, five active cigarette smokers, two dual users of e-cigarettes and cigarettes, and two sole users of e-cigarettes. All subjects were healthy individuals free of other major cardiovascular risk factors. The researchers examined the effects of e-liquids on endothelial cell viability by treating the iPSC-ECs with a dilution of six commercially available e-liquids at varying nicotine concentrations.

The researchers found all six flavored e-liquids had varying effects on cell survival and observed the presence of pro-inflammatory markers that are known to play a critical role in the development of vascular disease. The fruit-flavored, sweet tobacco with undertones of caramel and vanilla flavored, tobacco-flavored Red Oak Tennessee Cured, and sweet-flavored Butter Scotch all had moderate toxic effects on the cells, with the strongest toxic effect coming from the cinnamon-flavored Marcado. They also found menthol tobacco-flavored Tundra had a strong toxic effect at 1 percent dose of concentration with or without nicotine.

The researchers also found that the use of e-cigarettes may increase plasma nicotine concentrations to similar levels found with the use of conventional cigarettes, indicating that e-cigarettes provide effective and measurable nicotine delivery.

"Although limited by a small sample size, our data suggest that e-cigarette use can lead to acute endothelial dysfunction, which we validated by in vitro exposure to either e-liquid or serum derived from patients using e-cigarettes," said Joseph C. Wu, MD, PhD, FACC, the study's senior author. "E-cigarette use in the U.S. and worldwide is rapidly increasing with growing concerns from the scientific, public health and policy making communities. Our findings are an important first step in filling this gap by providing mechanistic insights on how e-cigarettes cause endothelial dysfunction, which is an important risk factor for the development of heart disease."

In an accompanying editorial comment, Jane E. Freedman, MD, and Chinmay M. Trivedi, MD, PhD, add that moving forward, "additional product and safety testing appear necessary to clarify the dangerous components of these products."

Keywords: Tobacco, Nicotine, Menthol, Risk Factors, Induced Pluripotent Stem Cells, Cardiovascular Diseases, Tobacco Products, Flavoring Agents, Policy Making, Vascular Diseases, Endothelial Cells, Heart Diseases

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