Peer-Reviewed 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

      Poussin, C.; Laurent, A.; Kondylis, A.; Marescotti, D.; van der Toorn, M.; Guedj, E.; Goedertier, D.; Acali, S.; Pak, C.; Dulize, R.; Baumer, K.; Peric, D.; Maluenda, E.; Bornand, D.; Suarez, I. G.; Schlage, W. K.; Ivanov, N. V.; Peitsch, M. C.; Hoeng, J.
      Published
      Jul 17, 2018
      DOI
      10.1016/j.fct.2018.07.025
      PMID
      30026091
      Topic
      Summary

      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 arterial endothelial cells (HCAEC) were treated for 4h with conditioned media from monocytic Mono Mac 6 (MM6) cells exposed to CHTP1.2 or 3R4F extracts for 2h 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.