E-cigarette use alters the epigenetic landscape of circulating monocytes in a sex-specific manner 3219

Abstract Description E-cigarette (e-cig) use has increased substantially but the health effects are poorly understood. E-cig vapor contains nicotine like tobacco cigarette smoke, which is known to increase the risk of cardiovascular disease (CVD), in part via monocyte activation. Functional differences in monocytes from males and females with CVD have been reported. Thus, we hypothesized that e-cigarette exposure activates monocytes, with a greater effect in females. We recruited 10 e-cig users (EC; 5F/5M) and 12 healthy controls (HC; 7F/5M) with no history of e-cig use, quantified circulating monocyte subsets, and performed bulk ATACseq and RNAseq on purified CD14+CD16- classical monocytes (CM). Compared to HC, EC had lower frequencies of CM (p < 0.05) and higher frequencies of CD14-CD16+ nonclassical monocytes (NCM p < 0.05), but no sex differences were observed. ATACseq identified 16,508 differentially accessible chromatin regions (DAR) in female EC vs HC and 8,744 DAR in female vs male EC. Of these, over 60% of these are located near the promoter region. Additionally, GeneOntology analysis revealed enriched pathways in female HC associated with myeloid cell differentiation and antigen processing. RNAseq analysis identified altered gene expression of functional monocyte genes. Our results indicate NCM are increased in female EC, which has been associated with CVD. Further, functional differences in monocytes from female EC may become apparent with maturation or interactions with the endothelium. Funding Sources Supported by NIH T32AI007485: NIH ES005605-32; University of Iowa Lulu Merle Fellowship, University of Iowa Inflammation Program Topic Categories Innate Immune Responses and Host Defense: Cellular Mechanisms (INC)