title: 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.
authors.affiliation: Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland. Electronic address: Justyna.Szostak@pmi.com.
authors.forename: Justyna
authors.initials: J
authors.lastname: Szostak
authors.affiliation: Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland. Electronic address: Stephanie.Boue@pmi.com.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Boué
authors.affiliation: Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland. Electronic address: Marja.Talikka@pmi.com.
authors.forename: Marja
authors.initials: M
authors.lastname: Talikka
authors.affiliation: Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland. Electronic address: Emmanuel.Guedj@pmi.com.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Guedj
authors.affiliation: Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland. Electronic address: Florian.Martin@pmi.com.
authors.forename: Florian
authors.initials: F
authors.lastname: Martin
authors.affiliation: Philip Morris International Research Laboratories Pte Ltd, Science Park II, Singapore. Electronic address: Blaine.Phillips@pmi.com.
authors.forename: Blaine
authors.initials: B
authors.lastname: Phillips
authors.affiliation: Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland. Electronic address: Nikolai.Ivanov@pmi.com.
authors.forename: Nikolai V
authors.initials: NV
authors.lastname: Ivanov
authors.affiliation: Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland. Electronic address: Manuel.Peitsch@pmi.com.
authors.forename: Manuel C
authors.initials: MC
authors.lastname: Peitsch
authors.affiliation: Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland. Electronic address: Julia.Hoeng@pmi.com.
authors.forename: Julia
authors.initials: J
authors.lastname: Hoeng
mesh_terms: D000336:Aerosols / Q000008:administration & dosage / Q000009:adverse effects* / Q000032:analysis; D000818:Animals; D001057:Apolipoproteins E / Q000502:physiology; D015415:Biomarkers / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000209:etiology; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D053263:Gene Regulatory Networks / Q000187:drug effects; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D019570:Inhalation Exposure; D051379:Mice; D018345:Mice, Knockout; D012906:Smoke / Q000009:adverse effects* / Q000032:analysis; D062789:Tobacco Products / Q000009:adverse effects* / Q000032:analysis
chemical_list: D000336:Aerosols; D001057:Apolipoproteins E; D015415:Biomarkers; D012906:Smoke
keywords: Apoe-/- mice; Cardiac muscle; Cigarette smoke; Contraction; Heart; Inflammation