Cigarette smoking (CS) is the main preventable cause of chronic obstructive pulmonary disease (COPD) and lung cancer. Research of potentially less harmful nicotine delivery devices and tools for smoking cessation resulted in the development of electronic cigarettes (e-cigarette). Despite the lack of appropriate studies regarding their safety, efficacy and health effects, e-cigarettes are gaining popularity as an approach of CS cessation and the number of e-cigarettes users is rapidly growing worldwide, especially among younger generations. Against this background, the aim of the current study was to investigate the effects of e-cigarette vapour extract (ECVE) on a cytotoxicity, cellular functions and gene expressions in different human cell lines (adenocarcinoma cell line [A549] and human bronchial epithelial cells [HBEpCs]), primary mouse cells (murine alveolar epithelial typeII cells [mAECII] and pulmonary arterial smooth muscle cells [mPASMCs]) and human lung cells (human pulmonary arterial smooth muscle cells [hPASMCs]) as well as to study the long-term effects of e-cigarette vapour on the function and structure of mouse lung and pulmonary circulation in vivo.Regardless of nicotine, ECVE showed a little (A549, mAECII, and hPASMCs) or no effect (HBEpCs and mPASMCs) on the cell viability compared to the cigarette smoke extract (CSE). Furthermore, ECVE with (18mg/ml) or without nicotine did not alter the cellular respiration of mPASMC as well as the migration of hPASMC and mPASMC. However, only nicotine containing ECVE decreased the proliferation of hPASMC and mPASMC compared to ECVE without nicotine. The hypothesis driven approach showed increased mRNA expression of iNOS, Csf2, 5HTT and Ccna1 in mPASMC after exposure to ECVE with nicotine indicating their possible roles in ECVE nicotine-induced decrease of mPASMC proliferation. Non-hypothesis driven transcriptomic analysis by microarray revealed that genes related to cell cycle, DNA replication and spliceosome were upregulated, while genes of lysosome and metabolic pathways were downregulated in mPASMCs exposed to ECVE regardless of nicotine. Moreover, various metabolic pathways, particularly genes involved in cytochrome P450 and glutathione metabolism were upregulated in mAECII. Exposure of wild type mice (C57BL/6J) to e-cigarette vapour with (18mg/ml) or without nicotine for 8 months (6 hours/day, 5 days/week) did not result in development of neither lung emphysema nor pulmonary hypertension assessed by lung function, hemodynamic and morphological analysis, respectively. However, long-term exposure to e-cigarette vapour evoked changes in the neutrophils, lymphocytes and macrophages amounts in bronchoalveolar lavage fluid indicating that e-cigarette vapour could induce the alteration of immune cell dynamics in the mouse lungs.In conclusion, despite that ECVE is less cytotoxic compared to CSE, exposure to ECVE alters nicotine-independently various cellular signalling pathways in lung cells in vitro. Moreover, even though long-term exposure of mice to e-cigarette vapour does not show any functional and structural alterations in the lungs, similar to conventional CS, exposure to e-cigarette prompts the distinct inflammatory responses in the mouse lung. Further experiments are necessary to elucidate the effects of various puffing regimen parameters (e-cigarette topography) and especially the presence of numerous flavours in e-cigarette liquids on the human health.
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