Aerosol from Tobacco Heating System 2.2 has reduced impact on mouse heart gene expression compared with cigarette smoke

Abstract

Experimental studies clearly demonstrate a causal effect of cigarette smoking on cardiovascular disease. To reduce the individual risk and population harm caused by smoking, alternative products to cigarettes are being developed. We recently reported on an apolipoprotein E-deficient (Apoe) mouse inhalation study that compared the effects of exposure to aerosol from a candidate modified risk tobacco product, Tobacco Heating System 2.2 (THS2.2), and smoke from the reference cigarette (3R4F) on pulmonary and vascular biology. Here, we applied a transcriptomics approach to evaluate the impact of the exposure to 3R4F smoke and THS2.2 aerosol on heart tissues from the same cohort of mice. The systems response profiles demonstrated that 3R4F smoke exposure led to time-dependent transcriptomics changes (False Discovery Rate (FDR) < 0.05; 44 differentially expressed genes at 3-months; 491 at 8-months). Analysis of differentially expressed genes in the heart tissue indicated that 3R4F exposure induced the downregulation of genes involved in cytoskeleton organization and the contractile function of the heart, notably genes that encode beta actin (Actb), actinin alpha 4 (Actn4), and filamin C (Flnc). This was accompanied by the downregulation of genes related to the inflammatory response. None of these effects were observed in the group exposed to THS2.2 aerosol.

New ideas, old problems? Heated tobacco products – a systematic review

“…Most in vivo studies were performed on apolipoprotein E-deficient (Apoe -/-) mouse models exposed to cigarette smoke or the IQOS aerosol for 8 months (Table 2). In contrast to traditional cigarette smoke, IQOS aerosols did not affect the downregulation of genes involved in the cytoskeleton organization, contractile function of the heart, or genes related to the inflammatory responses [64]. The IQOS aerosol had reduced biological effects on the livers of the Apoe -/mice [65].…”

Comparing the preclinical risk profile of inhalable candidate and potential candidate modified risk tobacco products: A bridging use case

“…Exposure to 3R4F CS, in both studies, induced differential expression of approximately 550–580 genes in the myocardial tissue ( Fig. 10 C); many of these differentially expressed genes were downregulated, including genes related to inflammatory responses and cytoskeletal and structural integrity, while those related to amino acids and xenobiotic metabolism were upregulated [ 62 , 91 ]. In contrast, no significant differential gene expression was observed in the heart in mice exposed to THS 2.2 or CHTP 1.2 aerosol ( Fig.…”

“… THS 2.2 [ 56 ] 3 Standard genotoxicity and cytotoxicity In vitro neutral red, Ames, and mouse lymphoma assays. CHTP 1.2 2,3,4 OECD rat THS 2.2 Nose-only 90-day OECD rat study 3R4F, THS 2.2 [ 58 ] 2,3,4 OECD rat CHTP 1.2 Nose-only 90-day OECD rat study 3R4F, CHTP 1.2 (Phillips et al; Titz et al) 2,3,4,5 ApoE −/− mice #1 Whole-body 8-month ApoE −/− study (+ switch/cessation after 2 months) 3R4F, THS 2.2 [ [59] , [60] , [61] , [62] , [63] ] 2,3,4,5 ApoE −/− mice #2 Whole-body 6-month ApoE −/− study (+ switch/cessation after 3 months) 3R4F, THS 2.2, CHTP 1.2 [ 64 ] 3,4 Organotypic nasal THS 2.2 In vitro exposure of organotypic nasal cultures at the air–liquid interface THS 2.2 [ 65 ] 3,4 Organotypic nasal CHTP 1.2 In vitro exposure of organotypic nasal cultures at the air–liquid interface CHTP 1.2 [ 66 ] 3,4 Organotypic small airway THS 2.2 In vitro exposure of organotypic small airway cultures at the air–liquid interface THS 2.2 [ ...…”

Carbonyl emissions from a novel heated tobacco product (IQOS): comparison with an e‐cigarette and a tobacco cigarette

“…This is expected to result in lower levels of toxic emissions and, as a result, they are marketed as reduced‐risk products. Several studies have assessed the chemistry and toxicology of this and other similar products from other manufacturers . However, with few exceptions , all studies have been performed by the manufacturers of the products.…”