E-cigarette vapor containing nicotine increases aortic stiffness in young and adult mice

Background and aims: E-cigarettes (E-cigs) are widely used especially among young people, but the effects on vascular stiffening and remodeling are poorly understood. This study evaluates the effects of short-term e-cig exposure on young vs. adult mice and the effects of e-cig derived chemicals present in plasma and urine of exposed animals on cultured endothelial cells (EC) and vascular smooth muscle cells (SMC). Methods C57BL/6J mice of 6- and 14-weeks of age were exposed to unflavored e-cig vapor with and without nicotine and aortic tissue subjected to in- and ex-vivo assessment of stiffness and histological evaluation. Major chemical constituents of e-cig vapor were analyzed in plasma and urine samples, and cultured human aortic ECs and SMCs were treated with these chemicals, including acrolein, formaldehyde and nicotine. Changes in gene and protein expression were quantified, and functional ROS and MMP assays were performed. Results Pulse wave velocity and ex-vivo myography revealed increased stiffness upon treatment with e-cig vapor, and to a greater extent with the inclusion of nicotine. Aortic elastin content in these mice was decreased when compared to room-air controls. In vitro treatment with some of the different chemical compounds present in e-cig vapor led to an increase in endothelial activation markers, and extracellular remodeling proteins. Wire myography showed an endothelium-independent decrease in relaxation in young murine aortas treated with nicotine. Conclusion Our results indicate that even brief exposure to e-cig vapor leads to marked changes in aortic stiffness and vascular remodeling, potentially predisposing for cardiovascular disease conditions, especially when started at an early age.