Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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The impact of long term cigarette smoke, but not Tobacco Heating System 2.2 exposure on the genes involved in cardiac muscle structure and function in Apoe-/- mouse.

ABSTRACT: Cigarette smoking is a major risk factor for the development and progression of diseases such as cardiovascular disease (CVD) and chronic obstructive pulmonary disease (COPD). Modified risk tobacco products (MRTP) are designed to reduce smoking-related health risks. Suitable animal models are important for understanding smoke-induced pathogenesis. Over an 8-month period, hallmarks of CVD were investigated in ApoE?/? mice exposed to conventional cigarette smoke (CS) or to an aerosol from a candidate RRP, the tobacco heating system (THS2.2). In addition to chronic exposure, cessation or switching to THS2.2 after 2 months of CS were investigated.ﾠ The aim of this study was to evaluate the transcriptomics response of mouse heart tissue after exposure to 3R4F and a potential reduced risk tobacco product, Tobacco Heating System 2.2 (THS2.2). The transcriptomic analysis of heart tissue, showed that cigarette smoke strongly impacted the differential expression of genes at long term of smoke exposure at 6 and 8 month, whereas the new THS2.2 not burning product donﾒt present any significant impact on the genes expression on cardiovascular tissue. In a similar manner, cessation and switching exposure donﾒt present any significant regulation of genes. Functional analysis of differentially expressed genes shown that 3R4F exposure strongly regulate the cytoskeleton organization and contraction and shown a down regulation of actin, actinin alpha 4, the main component of sarcomere structure. These preliminary results suggest that the conventional smoking product may favours the development of cardiomyopathy via a direct impact of the cardiomyocytes structure and that the inflammatory process could also be affected by the smoke exposure and could be responsible for the non-adaptive response of heart to a stress.

ORGANISM(S): Mus musculus

SUBMITTER: Vincenzo Belcastro

PROVIDER: E-MTAB-3900 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Besides its well-known effects increasing predisposition to oral cancer, cigarette smoke (CS) exposure is an important risk factor for many conditions including periodontal diseases, gingivitis and other benign mucosal disorders. Smoking cessation remains the most effective approach for minimizing risk of smoking-related diseases. However, reduction of harmful constituents by heating rather than combusting tobacco, without modifying the amount of nicotine, is a promising new paradigm in harm reduction. In this study we compared effects of exposure to aerosol derived from a candidate modified risk tobacco product, the tobacco heating system (THS) 2.2, with those of conventional smoke generated from the 3R4F reference cigarette. Human organotypic oral epithelial tissue cultures (EpiOralï¾, MatTek Corporation) were exposed for 28 min to 3R4F CS or THS2.2 aerosol, both diluted with air to comparable nicotine concentrations (0.32 or 0.51 mg nicotine/L aerosol/smoke for 3R4F and 0.31 or 0.46 mg/L for THS2.2). We also tested one higher concentration (1.09 mg/L) of THS2.2. A systems toxicology approach was employed combining cellular assays (i.e. cytotoxicity and cytochrome P450 activity assays), comprehensive molecular investigations of the buccal epithelial transcriptome (mRNA and miRNA) by means of computational network biology, measurements of secreted proinflammatory markers, histopathological analysis. We observed that the impact of 3R4F CS was greater than THS2.2 aerosol in terms of cytotoxicity, morphological tissue alterations and secretion of inflammatory mediators. Analysis of the transcriptomic changes in the exposed oral cultures revealed significant perturbations in various network models such as apoptosis, necroptosis, senescence, xenobiotic metabolism, oxidative stress and nuclear factor (erythroid-derived 2)-like 2 (NFE2L2) signaling. The stress responses following THS2.2 aerosol exposure were markedly decreased and the exposed cultures recovered better as compared with those exposed to 3R4F CS.

Dataset Information

The impact of long term cigarette smoke, but not Tobacco Heating System 2.2 exposure on the genes involved in cardiac muscle structure and function in Apoe-/- mouse.

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