Dataset Information

Use of Apoe−/− Mice in an 8-Month Systems Toxicology Inhalation/Cessation Study to Investigate Cardiovascular and Respiratory Exposure Effects of a Candidate Modified Risk Tobacco Product, THS 2.2, Compared with Conventional Cigarettes

ABSTRACT: Cigarette smoking is a major risk factor for the development and progression of cardiovascular disease (CVD) and chronic obstructive pulmonary disease (COPD), so modified risk tobacco products (MRTPs) are being developed to reduce smoking-related health risks. The present study investigated the hallmarks of COPD and CVD over an 8-month period in apolipoprotein E-deficient mice exposed to conventional cigarette smoke (CS) or to an aerosol from a candidate MRTP, the tobacco heating system (THS2.2). In addition to chronic exposure, cessation or switching to THS2.2 after 2 months of CS was investigated. In a systems toxicology approach, exposure effects were investigated using physiology and histology combined with transcriptomics, lipidomics, and proteomics. CS induced nasal epithelial hyperplasia and metaplasia, lung inflammation, and emphysematous changes (impaired pulmonary function and alveolar damage). Atherogenic effects of CS exposure included altered lipid profiles and increased aortic plaque formation. Exposure to THS2.2 aerosol (nicotine concentration matched to CS: 29.9 mg/m3) did not induce lung inflammation or emphysema, nor did it consistently change the lipid profile or enhance the plaque area. Cessation and switching reversed the inflammatory responses and led to no further progression of initial emphysematous changes or the aortic plaque area. Biological processes, including senescence, inflammation, and proliferation, were significantly impacted in CS, but not THS2.2-exposed tissues. Cessation or switching reduced these perturbations to become nearly indistinguishable from sham exposure. In conclusion, this mouse model indicated that cessation or switching to THS2.2 retarded the progression of atherosclerotic and emphysematous changes, while THS2.2 alone had no adverse effects.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Lung

SUBMITTER: Bjoern Titz

LAB HEAD: Julia Hoeng

PROVIDER: PXD002530 | Pride | 2015-11-30

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	20140710_150153_CNU_04_ApoE_Month8_Set_3_sensitive_140712070133.raw	Raw
	20140710_150153_CNU_05_ApoE_Month8_Set_3_fast.raw	Raw
	20140710_150153_CNU_06_ApoE_Month1_Set_1_fast.raw	Raw
	20140710_150153_CNU_07_ApoE_Month3_Set_5_sensitive.raw	Raw
	20140710_150153_CNU_08_ApoE_Month1_Set_1_sensitive.raw	Raw

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An 8-Month Systems Toxicology Inhalation/Cessation Study in Apoe-/- Mice to Investigate Cardiovascular and Respiratory Exposure Effects of a Candidate Modified Risk Tobacco Product, THS 2.2, Compared With Conventional Cigarettes.

Phillips Blaine B Veljkovic Emilija E Boué Stéphanie S Schlage Walter K WK Vuillaume Gregory G Martin Florian F Titz Bjoern B Leroy Patrice P Buettner Ansgar A Elamin Ashraf A Oviedo Alberto A Cabanski Maciej M De León Héctor H Guedj Emmanuel E Schneider Thomas T Talikka Marja M Ivanov Nikolai V NV Vanscheeuwijck Patrick P Peitsch Manuel C MC Hoeng Julia J

Toxicological sciences : an official journal of the Society of Toxicology 20151125 2

Smoking cigarettes is a major risk factor in the development and progression of cardiovascular disease (CVD) and chronic obstructive pulmonary disease (COPD). Modified risk tobacco products (MRTPs) are being developed to reduce smoking-related health risks. The goal of this study was to investigate hallmarks of COPD and CVD over an 8-month period in apolipoprotein E-deficient mice exposed to conventional cigarette smoke (CS) or to the aerosol of a candidate MRTP, tobacco heating system (THS) 2.2 ...[more]

PMID: 26609137

Publication: 1/2

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