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In vitro systems toxicology-based assessment of the potential modified risk tobacco product CHTP1.2 for vascular inflammation- and cytotoxicity-associated mechanisms promoting adhesion of monocytic cells to human coronary arterial endothelial cells.

ABSTRACT: Cigarette smoke causes diseases such as cardiovascular disorders. Heating tobacco, instead of burning, reduces consistently the amount of toxic compounds and may exert a reduced impact on cardiovascular health compared to cigarettes. Aqueous extract from the aerosol of a potential modified risk tobacco product, the carbon-heated tobacco product (CHTP) 1.2 was assessed in vitro for its impact, compared with a reference cigarette (3R4F), on a key mechanism of atherosclerosis, the adhesion of monocytic cells to artery endothelial cells. Human coronary arterial endothelial cells (HCAECs) were treated for 4h with conditioned media from monocytic Mono Mac-6 (MM6) cells exposed to the aqueous aerosol/smoke extracts for 2h (Indirect exposure) or directly with those extracts freshly generated (Fresh Direct exposure). Using a previously established in vitro adhesion assay design, MM6-HCAEC adhesion combined with inflammatory, oxidative stress, cytotoxicity and cell death markers was measured. The 3R4F extract promoted the adhesion of MM6 cells to HCAECs via distinct inflammatory- and cytotoxicity-driven mechanisms. In conclusions, our systems toxicology study demonstrated that approximately 10-15-fold higher concentrations of the CHTP1.2 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.

ORGANISM(S): Homo sapiens

SUBMITTER: Alain Sewer

PROVIDER: E-MTAB-6721 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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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.

Poussin Carine C Laurent Alexandra A Kondylis Athanasios A Marescotti Diego D van der Toorn Marco M Guedj Emmanuel E Goedertier Didier D Acali Stefano S Pak Claudius C Dulize Rémi R Baumer Karine K Peric Dariusz D Maluenda Elodie E Bornand David D Suarez Ignacio Gonzalez IG Schlage Walter K WK Ivanov Nikolai V NV Peitsch Manuel C MC Hoeng Julia J

Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 20180717

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 ce ...[more]

PMID: 30026091

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Project description:Cigarette smoke (CS) has been reported to affect the adhesion of monocytes to endothelial cells, a critical step in atherogenesis. Using an in vitro adhesion assay together with innovative computational systems biology approaches to analyze omics data, our study aimed at investigating CS-induced mechanisms by which monocyte-endothelial cell adhesion is promoted. Disease-relevant primary human coronary artery endothelial cells (HCAECs) were treated for 4 hours with (1) conditioned media of human monocytic Mono Mac-6 (MM6) cells preincubated with low or high concentrations of aqueous CS extract (sbPBS) from reference cigarette 3R4F for 2 hours (indirect treatment, I), (2) unconditioned media similarly prepared, however without MM6 cells (direct treatment, D), or (3) freshly generated sbPBS (fresh direct treatment, FD). sbPBS promoted MM6 cells-HCAECs adhesion following I and FD, but not D. In I, the effect was mediated at a low concentration through activation of vascular inflammation processes promoted in HCAECs by a paracrine effect of the soluble mediators secreted by sbPBS-treated MM6 cells. Tumor necrosis factor alpha (TNF-alpha major inducer, was actually shed by unstable CS compound-activated TNFalpha-converting enzyme. In FD, the effect was triggered at a high concentration that also induced some toxicity. This effect was mediated through an yet unknown mechanism associated with a stress damage response promoted in HCAECs by unstable CS compounds present in freshly generated sbPBS, which had decayed in D unconditioned media. In conclusion, aqueous CS extract directly and indirectly promotes monocytic cell-endothelial cell adhesion in vitro via distinct concentration-dependent mechanisms. Samples from E-MTAB-3644 dataset correspond to 3R4F sbPBS15 and PBS15 (vehicle control: 15% v/v). In the E-MTAB-3923 dataset, samples correspond to THS2.2 abPBS15, THS2.2 abPBS75 and PBS75 (75% v/v). All THS2.2 abPBS15 from E-MTAB-3923 must be compared with their respective control, PBS15 from E-MTAB-3644; while THS2.2 abPBS75 from E-MTAB-3923 must be compared with their respective control, PBS75 from E-MTAB-3923.

Dataset Information

In vitro systems toxicology-based assessment of the potential modified risk tobacco product CHTP1.2 for vascular inflammation- and cytotoxicity-associated mechanisms promoting adhesion of monocytic cells to human coronary arterial endothelial cells.

Publications

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.

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