PXD002530

PXD002530 is an original dataset announced via ProteomeXchange.

Title	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
Description	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.
HostingRepository	PRIDE
AnnounceDate	2015-11-30
AnnouncementXML	Submission_2015-11-30_05:17:57.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Bjoern Titz
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue; TMT6plex-126 reporter+balance reagent acylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2015-07-13 05:11:08	ID requested
1	2015-11-30 04:30:16	announced
⏵ 2	2015-11-30 05:17:58	announced	Updated publication reference for PubMed record(s): 26582801, 26609137.

Phillips B, Veljkovic E, Bou, é S, Schlage WK, Vuillaume G, Martin F, Titz B, Leroy P, Buettner A, Elamin A, Oviedo A, Cabanski M, De Le, ó, n H, Guedj E, Schneider T, Talikka M, Ivanov NV, Vanscheeuwijck P, Peitsch MC, Hoeng J, 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. Toxicol Sci, 149(2):411-32(2016) [pubmed]

Titz B, Bou, é S, Phillips B, Talikka M, Vihervaara T, Schneider T, Nury C, Elamin A, Guedj E, Peck MJ, Schlage WK, Cabanski M, Leroy P, Vuillaume G, Martin F, Ivanov NV, Veljkovic E, Ekroos K, Laaksonen R, Vanscheeuwijck P, Peitsch MC, Hoeng J, Effects of Cigarette Smoke, Cessation, and Switching to Two Heat-Not-Burn Tobacco Products on Lung Lipid Metabolism in C57BL/6 and Apoe-/- Mice-An Integrative Systems Toxicology Analysis. Toxicol Sci, 149(2):441-57(2016) [pubmed]

curator keyword: Biomedical

submitter keyword: mouse, cigarette smoke, modified risk tobacco product, lung

Julia Hoeng
contact affiliation	Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland
contact email	julia.hoeng@pmi.com
lab head
Bjoern Titz
contact affiliation	Philip Morris International R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchâtel, Switzerland
contact email	bjorn.titz@pmi.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD002530
     1. Label: PRIDE project
     2. Name: 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