Effects of an In Vivo Vaping Challenge on In Vitro IL-6 Biosynthesis Pathways in Arterial Endothelial Cells Derived from Human Embryonic Stem Cells

Electronic nicotine delivery system (ENDs) use among youth and young adults is increasing at a rapid pace and represents a growing public health threat.1 Newer generation devices heat e-liquids to higher temperatures and can achieve higher serum nicotine concentrations than older devices.1 Interleukin-6 (IL-6) is a cytokine that mediates atherogenesis and independently predicts future atherosclerotic cardiovascular disease events.2 Previous in vitro studies have demonstrated increased IL-6 production by human alveolar macrophages exposed to ENDs condensate.3 Although there has been considerable focus on the effects of ENDs use on airway inflammation, there are a paucity of data on the effects of ENDS on arterial inflammation. Prior in vitro studies used venous endothelial cells (VECs) or human umbilical VECs as a proxy for arterial endothelial cells (AECs), limiting generalizability of their findings. Historically, use of AECs was limited by the invasive collection methods. We used a novel in vitro AEC model of human embryonic stem-cell-derived AECs to study differential expression (DE) of IL-6 pathway genes after exposure to serum from human participants taken before and after vaping using 3rd or 4th generation ENDs or no product use. Overall design: We randomly selected serum from 10 chronic, exclusive ENDs users (exhaled carbon monoxide <5 ppm, positive urine nicotine) and 10 non-vaping, non-smoking controls from the Cardiac and LUng E-cigarette Smoking Study (CLUES, NCT03863509). ENDs users abstained from product use for >8 hours prior to the study visit. Participants completed a 15-minute ad libitum product use challenge in a dedicated room with external ventilation under remote supervision by a trained observer. ENDs users vaped with their ENDs product and controls rested. Post-challenge serum was collected in ENDs users 15-minutes after the product use challenge.