Abstract 12948: Both Electronic and Regular Cigarettes Induce Transcriptional Changes in iPS-Derived Cardiomyocytes

Abstract

Introduction: Cigarette smoking is an important etiology for cardiac diseases and electronic cigarettes are increasing in popularity. In the current study, we sought to assess differential gene expression in iPS-cardiomyocytes after exposure to conventional cigarette smoke extract (CSE) and electronic cigarette extracts (ECE) utilizing direct digital mRNA detection of heart failure targeted genes. Hypothesis: Methods: Human cardiomyocytes derived from iPSCs were acutely exposed for two consecutive days with 2.5% of CSE and ECE. RNAs were isolated and NanoString analysis was used to compare gene expression between groups for 126 heart failure specific genes. NanoString mRNA raw count data were preprocessed and normalized using nSolver 4.0 Analysis SoftwareNano-string of customized target panel was run for mRNA expression of cardiomyocytes with direct exposure to CSE (N=3) and ECE (N=3) and was compared to control (N=3). At least a 1.5-fold change in gene expression with FDR adjusted p<0.05 was considered as significant. Results: Five genes were significantly differentially expressed cardiomyocytes exposed to CSE vs control (CETP, ATRLN1, ENOS, C10ORF88 and ERF). In ECE exposed cells, five genes were also significantly differentially expressed compared to control (PDK4, CAV3, PER1, MYH6 and ERF). ERF gene is a transcription factor and protooncogene involved in development, apoptosis, and the regulation of telomerase was significantly overexpressed in cells exposed to both CSE and ECE. Despite different nicotine concentrations in ECE and CSE, no significant gene differences between CSE and ECE were observed. Conclusions: ECE and CSE exposure alters transcriptional profiles in iPS-cardiomyocytes compared to controls in heart failure targeted genes. These genes are involved in transcription and circadian regulation, metabolism and contractile proteins. There were no significant differences in transcriptional profiles between ECE and CSE exposed cells.