In vitro systems toxicology-based assessment of the potential modified risk tobacco product CHTP 1.2 for vascular inflammation- and cytotoxicity-associated mechanisms promoting adhesion of monocytic cells to human coronary arterial endothelial cells. (October 2018)

• Record Type: Journal Article
• Authors: Poussin, Carine; Laurent, Alexandra; Kondylis, Athanasios; Marescotti, Diego; van der Toorn, Marco; Guedj, Emmanuel; Goedertier, Didier; Acali, Stefano; Pak, Claudius; Dulize, Rémi; Baumer, Karine; Peric, Dariusz; Maluenda, Elodie; Bornand, David; Suarez, Ignacio Gonzalez; Schlage, Walter K.; Ivanov, Nikolai V.; Peitsch, Manuel C.; Hoeng, Julia
• Is Part Of: Food and chemical toxicology. Volume 120(2018)
• Page Start: 390
• Page End: 406
• Publication Date: 2018-10
• Subjects: Modified risk tobacco product -- Cigarette -- Monocyte -- Endothelial cell -- Adhesion -- Atherosclerosis; 7-AAD 7-Aminoactinomycin D -- BIF Biological Impact Factor -- CFA Cell Fate -- CHTP Carbon Heated Tobacco Product -- CPR Cell Proliferation -- CS Cigarette Smoke -- CST Cell Stress -- CVD Cardiovascular Disease -- DEG Differentially Expressed Gene -- FCS Fetal Calf Serum -- FD Fresh Direct (treatment) -- FDR False Discovery Rate -- GSH Glutathion -- HCAEC Human Coronary Artery Endothelial Cell -- HPHC Harmful and Potentially Harmful Constituent -- I Indirect (treatment) -- ICAM-1 Intercellular Adhesion Molecule 1 -- IPN Inflammatory Process Network -- LC/ESI-MS/MS Liquid Chromatography Electrospray Ionization Tandem Mass Spectrometry -- MM6 Mono Mac 6 -- MP Main Phase -- MRTP Modified Risk Tobacco Product -- NF-κB Nuclear Factor-Kappa B -- NPA Network Perturbation Amplitude -- PC Principal Component -- PCA Principal Component Analysis -- (R)BIF (Relative) Biological Impact Factor -- ROS Reactive Oxygen Species -- SM Starvation Medium -- SRP Systems Response Profile -- THS Tobacco Heating System -- TNF-α Tumor Necrosis Factor-Alpha -- TRA Tissue Repair and Angiogenesis -- VC Vehicle Control -- VIP Vascular Inflammatory Processes; Toxicology -- Periodicals; Food poisoning -- Periodicals; Food Poisoning -- Periodicals; Toxicology -- Periodicals; Toxicologie -- Périodiques; Intoxications alimentaires -- Périodiques; Food poisoning; Toxicology; Periodicals; Electronic journals; 615.9
• DOI: 10.1016/j.fct.2018.07.025
• Languages: English
• ISSNs: 0278-6915

Abstract

Abstract: Cigarette smoking causes cardiovascular diseases. Heating tobacco instead of burning it reduces the amount of toxic compounds in the aerosol and may exert a reduced impact on health compared with cigarette smoke. Aqueous extract from the aerosol of a potential modified risk tobacco product, the Carbon Heated Tobacco Product (CHTP) 1.2, was compared in vitro with aqueous extract from the smoke of a 3R4F reference cigarette for its impact on the adhesion of monocytic cells to artery endothelial cells. Human coronary artery endothelial cells (HCAEC) were treated for 4 h with conditioned media from human monocytic Mono Mac 6 (MM6) cells exposed to CHTP1.2 or 3R4F extracts for 2 h or directly with those extracts freshly generated. In vitro monocyte-endothelial cell adhesion was measured concomitantly with inflammatory, oxidative stress, cytotoxicity, and death markers. Furthermore, transcriptomics analyses enabled to quantify the level of perturbation in HCAECs, and provide biological interpretation for the underlying molecular changes following exposure to 3R4F or CHTP1.2 extract. Our systems toxicology study demonstrated that approximately 10–15-fold higher concentrations of the CHTP 1.2 aerosol extract were needed to elicit similar effects as the 3R4F smoke extract on cardiovascular disease-relevant inflammation and cytotoxicity-related mechanisms and markers investigated in vitro . Graphical abstract: Highlights: The development of innovative modified risk tobacco product (MRTP) is necessary for public health concerns. Heating rather than burning tobacco reduced the formation of toxic compound in the aerosol of CHTP 1.2, a potential MRTP. 3R4F reference cigarette smoke extract promotes the adhesion of monocytic cells to HCAECs, a key process in atherogenesis. CHTP1.2 aerosol extract compared with that of 3R4F showed reduced biological impact on vascular pathomechanisms.