The effects of pod‐based e‐liquids on vascular endothelial cell function

Abstract

The use of electronic (e-) cigarettes has rapidly risen in youth and young adults. Pod-based e-cigarettes represent a more evolved generation of these devices that are designed to deliver higher levels of nicotine. Despite their popularity, little is known about the cardiovascular toxicity imposed by the use of e-cigarettes. The JUUL brand of pod-based e-cigarettes holds the majority of market shares in the US. The purpose of this study was to evaluate the effects of four common JUUL pod flavors (Menthol, Mint, Mango and Virginia Tobacco), the product constituents propylene glycol (PG)/vegetable glycerol (VG) vehicle at 30:70 ratio and nicotine salt in 30:70 PG/VG on vascular endothelial cell function. We evaluated endothelial function (cell viability by TUNEL and nitric oxide bioavailability using DAF-2DA) in human aortic endothelial cells (HAECs) following a 90-minute exposure to JUUL pods at dilutions of 0.00001% to 1%. Flavored JUUL pod exposure induced at least 15% endothelial cell death at dilutions of 0.0001% for Menthol, 0.1% for Mint, 0.1-1% for Mango, and 0.0001-1% for Virginia Tobacco. Cells exposed to the PG/VG vehicle alone and in the presence of nicotine salt increased cell death to similar levels as the flavored JUUL pod exposures, suggesting that the vehicle may be an important source of toxicity. All flavored JUUL pods at a dilution of 0.0001% impaired A23187-stimulated nitric oxide in HAECs, suggestive of endothelial dysfunction. Our data suggests that exposure of endothelial cells to flavored JUUL pods results in cytotoxicity and impairs nitric oxide bioavailability, which may be relevant to cardiovascular toxicity. Ongoing experiments focus on the evaluation of oxidative stress and interleukin-6 expression in vascular endothelial cells. Future work will include evaluation of the effects of JUUL e-liquid heated fractions to identify fractions and specific chemical constituents that induce endothelial cell toxicity.