An in vitro assessment of the effects of electronic cigarette aerosol on human vascular cell viability and function
Conventional cigarette smoking remains the leading cause of preventable death worldwide, yet one in five people continue to smoke. Recently, electronic cigarettes have become the most popular alternative tobacco product among adults and the most popular tobacco product of any kind among middle and high school students. However, the full health consequences of electronic cigarette use remain unclear, particularly with respect to the vascular system. The majority of tobacco product-related pathologies possess a vascular component, and it is imperative to determine whether electronic cigarettes pose the same vascular risk. This study examined the effects of electronic cigarette aerosol on vascular cell viability and function in primary human vascular cell lines. The parameters tested were cell viability, DNA damage, generation of reactive oxygen species and nitric oxide, the type of cell death induced, migration, proliferation, and vascular network formation and growth. The results indicate that commercial electronic cigarette aerosol reduces endothelial cell viability, causes DNA breaks, generates reactive oxygen species, and induces endothelial cell death through both apoptotic and non-apoptotic pathways. Further, the non-apoptotic pathway is dependent on oxidative stress and can be prevented with anti-oxidant therapy. An analysis of electronic cigarette components revealed that flavoring compounds, nicotine, and the vegetable glycerol/propylene glycol electronic cigarette liquid base are all capable of modulating vascular cell response. The flavoring compounds 2,3-butanedione and 2,3-pentanedione are capable of inducing cell death in both endothelial and smooth muscle cells in a cell type and compound dependent fashion. These two compounds were also shown to inhibit endothelial nitric oxide synthesis. Vegetable glycerol/propylene glycol electronic cigarette base with or without nicotine was shown to have a positive effect on endothelial cell viability, a negative effect on smooth muscle cell viability, and modulate endothelial cell proliferation and network formation. No formation of electronic cigarette aerosol was found to alter endothelial cell migration. Taken together, these results indicate that electronic cigarette aerosol may be safer than conventional cigarette smoke, but it is by no means safe. Additional research and careful regulatory controls are needed as these products are poised to become the leading tobacco product for future generations.