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A 6-month systems toxicology inhalation study in ApoE−/− mice demonstrates reduced cardiovascular effects of E-vapor aerosols compared to cigarette smoke.

ABSTRACT: Smoking cigarettes is harmful to the cardiovascular system. Considerable attention has been paid to the reduced harm potential of alternative nicotine-containing inhalable products such as e-cigarettes. We investigated the effects of E-vapor aerosols or cigarette smoke (CS) on atherosclerosis progression, cardiovascular function, and molecular changes in the heart and aorta of female ApoE−/− mice. The mice were exposed to aerosols from three different E-vapor formulations: (1) carrier (propylene glycol and vegetable glycerol), (2) base (carrier and nicotine) or (3) test (base and flavor) or to CS from 3R4F reference cigarettes for up to 6 months. Concentrations of CS and base or test aerosols were matched at 35 µg nicotine/L. Exposure to CS, compared with sham-exposed fresh air controls, accelerated atherosclerotic plaque formation, while no such effect was seen for any of the three E-vapor aerosols. Molecular changes indicated disease mechanisms related to oxidative stress and inflammation in general, plus changes in calcium regulation, and altered cytoskeletal organization and microtubule dynamics in the left ventricle. While ejection fraction, fractional shortening, cardiac output, and isovolumic contraction time remained unchanged following E-vapor aerosols exposure, the nicotine-containing base and test aerosols caused an increase in isovolumic relaxation time similar to CS. A nicotine-related increase in pulse wave velocity and arterial stiffness was also observed, but it was significantly lower for base and test aerosols than for CS. These results demonstrate that in comparison with CS, E-vapor aerosols induce substantially lower biological responses associated with smoking-related cardiovascular diseases.

ORGANISM(S): Mus musculus

SUBMITTER: Alain Sewer

PROVIDER: E-MTAB-8578 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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A 6-month systems toxicology inhalation study in ApoE<sup>-/-</sup> mice demonstrates reduced cardiovascular effects of E-vapor aerosols compared with cigarette smoke.

Szostak Justyna J Wong Ee Tsin ET Titz Bjoern B Lee Tom T Wong Sin Kei SK Low Tiffany T Lee Kyeonghee Monica KM Zhang Jingjie J Kumar Ashutosh A Schlage Walter K WK Guedj Emmanuel E Phillips Blaine B Leroy Patrice P Buettner Ansgar A Xiang Yang Y Martin Florian F Sewer Alain A Kuczaj Arkadiusz A Ivanov Nikolai V NV Luettich Karsta K Vanscheeuwijck Patrick P Peitsch Manuel C MC Hoeng Julia J

American journal of physiology. Heart and circulatory physiology 20200124 3

Smoking cigarettes is harmful to the cardiovascular system. Considerable attention has been paid to the reduced harm potential of alternative nicotine-containing inhalable products such as e-cigarettes. We investigated the effects of E-vapor aerosols or cigarette smoke (CS) on atherosclerosis progression, cardiovascular function, and molecular changes in the heart and aorta of female apolipoprotein E-deficient (ApoE<sup>-/-</sup>) mice. The mice were exposed to aerosols from three different E-va ...[more]

PMID: 31975625

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Project description:A 7-month inhalation study in C57BL/6 mice was conducted to evaluate long-term respiratory toxicity of e-vapor aerosols compared to cigarette smoke and to assess the impact of smoking cessation or switching to an e-vapor product after 3 months of exposure to 3R4F cigarette smoke (CS). In this study, we performed a chronic inhalation (4 h/day, 5 d/week, up to 7 months) study in C57BL/6 mice using a commercial (MarkTen®) e-vapor product and a combustible reference cigarette (3R4F) using a Switching and Cessation study design. A commercial e-vapor product (MarkTen® device [version 2.6.8]; “Test Red”) was supplied by Altria Client Services LLC (Richmond, VA, USA). The Test Red formulation was composed of aerosol formers (propylene glycol [PG] and vegetable glycerol [VG]), ~4% nicotine by weight, and flavors (non-menthol). The 3R4F commercial reference cigarettes were purchased from the University of Kentucky (Lexington, KY). HEPA filtered air at the testing facility (Battelle, West Jefferson, OH) was used as Sham Control. General procedures for animal care and housing met the Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC) recommendations and requirements stated in the “Guide for Care and Use of Laboratory Animals” [National Research Council (NRC)] and approved by the Institutional Animal Care and Use Committee (IACUC). Female C57BL/6 mice were received from Charles River Kingston (Stone Ridge, NY). Test atmosphere was generated from smoking machines and delivered to the mice through a nose-only exposure system. The modified Cooperation Centre for Scientific Research Relative to Tobacco (CORESTA) Reference Method 81 regimen (55/30/5: a 55 ± 0.3 mL puff volume, a puff every 30 seconds, a 5-second puff duration) was used to generate e-vapor aerosol for 130 puffs/cartridge. Mainstream smoke from 3R4F cigarette was generated using a modified Health Canada Intense regimen (55/30/2: a 55 ± 0.3 mL puff volume, a puff every 30 seconds, a 2-second puff duration, and a near-square puff profile) for 8 puffs/cigarette. Female C57BL/6 mice (~10 weeks old) were randomly assigned based on body weight to one of five exposure groups: Sham Control, 3R4F CS, Test Red, Switching, and Cessation. Mice were exposed to 3R4F CS (550 µg/L TPM) or e-vapor aerosols (Test Red; 1100 µg/L TPM) via nose-only inhalation up to 4 h/day, 5 d/week for up to 7 months. After the first 3 months of exposure, groups of 3R4F CS mice were subjected to exposures of: (1) Test Red aerosol (“Switching”) or (2) filtered air (“Cessation”), while a group of mice continued to be exposed to 3R4F CS. Here, the protein expression data for lung tissue assessed by iTRAQ®-based quantitative proteomics is reported.

Dataset Information

A 6-month systems toxicology inhalation study in ApoE−/− mice demonstrates reduced cardiovascular effects of E-vapor aerosols compared to cigarette smoke.

Publications

A 6-month systems toxicology inhalation study in ApoE<sup>-/-</sup> mice demonstrates reduced cardiovascular effects of E-vapor aerosols compared with cigarette smoke.

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