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. 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.