• Chem. Biol. Interact. · Jan 2020

    Structural, functional, and molecular impact on the cardiovascular system in ApoE-/- mice exposed to aerosol from candidate modified risk tobacco products, Carbon Heated Tobacco Product 1.2 and Tobacco Heating System 2.2, compared with cigarette smoke.

    • Justyna Szostak, Bjoern Titz, Walter K Schlage, Emmanuel Guedj, Alain Sewer, Blaine Phillips, Patrice Leroy, Ansgar Buettner, Laurent Neau, Keyur Trivedi, Florian Martin, Nikolai V Ivanov, Patrick Vanscheeuwijck, Manuel C Peitsch, and Julia Hoeng.
    • PMI R&D, Philip Morris Products S.A, Quai Jeanrenaud 5, CH-2000, Neuchâtel, Switzerland. Electronic address: Justyna.Szostak@pmi.com.
    • Chem. Biol. Interact. 2020 Jan 5; 315: 108887.

    AimTo investigate the molecular, structural, and functional impact of aerosols from candidate modified risk tobacco products (cMRTP), the Carbon Heated Tobacco Product (CHTP) 1.2 and Tobacco Heating System (THS) 2.2, compared with that of mainstream cigarette smoke (CS) on the cardiovascular system of ApoE-/- mice.MethodsFemale ApoE-/- mice were exposed to aerosols from THS 2.2 and CHTP 1.2 or to CS from the 3R4F reference cigarette for up to 6 months at matching nicotine concentrations. A Cessation and a Switching group (3 months exposure to 3R4F CS followed by filtered air or CHTP 1.2 for 3 months) were included. Cardiovascular effects were investigated by echocardiographic, histopathological, immunohistochemical, and transcriptomics analyses.ResultsContinuous exposure to cMRTP aerosols did not affect atherosclerosis progression, heart function, left ventricular (LV) structure, or the cardiovascular transcriptome. Exposure to 3R4F CS triggered atherosclerosis progression, reduced systolic ejection fraction and fractional shortening, caused heart LV hypertrophy, and initiated significant dysregulation in the transcriptomes of the heart ventricle and thoracic aorta. Importantly, the structural, functional, and molecular changes caused by 3R4F CS were improved in the smoking cessation and switching groups.ConclusionExposure to cMRTP aerosols lacked most of the CS exposure-related functional, structural, and molecular effects. Smoking cessation or switching to CHTP 1.2 aerosol caused similar recovery from the 3R4F CS effects in the ApoE-/- model, with no further acceleration of plaque progression beyond the aging-related rate.Copyright © 2019. Published by Elsevier B.V.

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