CARDIORESPIRATORY IMPACT OF E-VAPOR AEROSOLS AND CIGARETTE SMOKE EXPOSURE IN THE APOE KNOCKOUT MOUSE MODEL

Abstract

Chronic exposure to cigarette smoke (CS) causes cardiorespiratory diseases in smokers. Considerable attention has been given to the reduced harm potential of alternative e-vapor products. ApoE-/- mice were used to evaluate lung inflammation, emphysematous changes, atherosclerosis development, and cardiovascular function upon chronic (6-month) exposure to fresh air (Sham), CS, or e-vapor aerosols. Mice were exposed to CS from 3R4F reference cigarettes or e-vapor aerosols generated using capillary aerosol generators from various e-liquids (“CARRIER” containing humectants [propylene glycol, glycerin], “BASE” containing humectants and nicotine, and “TEST” containing humectants, nicotine, and flavors) via a whole-body inhalation system. Exposure to CS at a nicotine concentration of 35 μg/L causes adverse effects on the lungs (including increased lung volume and inflammation), accelerates atherosclerotic plaque formation, and alters the cardiorespiratory transcriptome. CS exposure causes an impairment of both systolic and diastolic cardiac function, as assessed by ejection fraction, fractional shortening, isovolumic relaxation time, and E/A ratio. In comparison with CS, exposure to e-vapor aerosols lower atherosclerotic plaque formation, was associated with limited to absent inflammatory cells in the lung tissue, and induced substantially less molecular changes in cardiorespiratory transcriptomes. Ultrasound analysis highlighted that cardiac dysfunction and aortic stiffness were less prominent in nicotine-containing e-vapor aerosol-exposed groups than in the CS-exposed group. This study suggests that in comparison with CS, e-vapor aerosols induce substantially lower biological responses associated with smoking-related cardiovascular and pulmonary diseases.