An 8-Month Systems Toxicology Inhalation/Cessation Study in XXXX -/- @entity19 to Investigate Cardiovascular and Respiratory Exposure Effects of a Candidate Modified Risk @entity286 Product, THS 2.2, Compared with Conventional Cigarettes.

@entity286 @entity32 @entity6970 @entity55 @entity19 @entity73 @entity16 @entity1239 @entity2415 @entity4648 @entity2543 @entity1030 @entity2333 @entity731 @entity65
UNASSIGNED: Smoking cigarettes is a major risk factor in the development and progression of @entity65 ( @entity65 ) and @entity1030 ( @entity1030 ). Modified risk @entity286 products (MRTPs) are being developed to reduce smoking-related health risks. The goal of this study was to investigate hallmarks of @entity1030 and @entity65 over an 8-month period in @entity6970 -deficient @entity19 exposed to conventional cigarette smoke (CS) or to the aerosol of a candidate MRTP, THS2.2. In addition to chronic exposure, cessation or switching to THS2.2 after 2 months of CS exposure was assessed. Engaging a systems toxicology approach, exposure effects were investigated using physiology and histology combined with transcriptomics, lipidomics, and proteomics. CS induced @entity2543 and @entity4648 , @entity55 , and emphysematous changes ( @entity73 and @entity16 ). Atherogenic effects of CS exposure included altered lipid profiles and aortic plaque formation. Exposure to THS2.2 aerosol ( @entity1239 concentration matched to CS, 29.9 mg/m(3)) did not induce @entity55 or @entity2415 , nor did it consistently change the lipid profile or enhance the plaque area. Cessation or switching to THS2.2 reversed the inflammatory responses and halted progression of @entity2333 . Biological processes, including senescence, @entity32 , and proliferation, were significantly impacted by CS, but not by THS2.2 aerosol. Both, cessation and switching to THS2.2 reduced these perturbations to almost sham exposure levels. In conclusion, in this @entity19 model cessation or switching to THS2.2 retarded the progression of CS-induced @entity731 and emphysematous changes, while THS2.2 aerosol alone had minimal adverse effects.
