E-cigarette-induced changes in cell stress and mitochondrial function.

Abstract

Inhaling aerosols from electronic nicotine delivery systems, such as e-cigarettes (e-cigs), may pose health risks beyond those caused by nicotine intake. Exposure to e-cig aerosols can lead to the release of exosomes and metabolites into the bloodstream, potentially affecting mitochondrial physiology across the body, leading to chronic inflammatory diseases. In this study we assessed the effects of e-cig use by young healthy human subjects on the circulating exosome profile and markers of cell stress, and also defined the effects of e-cig user plasma on mitochondrial function in endothelial cells (EA. Hy 926) and epithelial cells (A549) via adoptive transfer. E-cig users had altered plasma exosome profiles, with significantly increased levels of cell free mitochondrial DNA (mtDNA), protein carbonyls, and 4-HNE relative to non-users. Plasma from e-cig users decreased maximal mitochondrial respiration and spare capacity of cells, while also increasing metabolic stress, as evidenced by changes in mitochondrial phenotype from basal to stressed in both endothelial and epithelial cells, which was corroborated by electron microscopy demonstrating structural changes in mitochondria. Mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) levels significantly increased in e-cig plasma-subjected cells. Overall, we identified alterations in plasma exosome profiles and increased markers of mitochondrial stress in e-cig users and evidence that circulating factors within plasma from e-cig users drives metabolic stress in endothelial and epithelial cells. Our results imply that e-cig use adversely affects mitochondrial function, leading to stress and potentially chronic inflammation across the body.