Systems toxicology-based assessment of the candidate modified risk tobacco product ThS2.2 for the adhesion of monocytic cells to human coronary arterial endothelial cells

Introduction:
This study compares the effects of aqueous extracts from a candidate modified risk tobacco product (ThS2.2) and a reference cigarette (3R4F) on the adhesion of monocytic cells to primary human endothelial cells. The approach combines functional measurements with transcriptomics and inflammatory protein marker data to investigate cellular changes at the molecular level in both MM6 cells and hCaECs.

Key Points:

* The study found that ThS2.2 aerosol extract had significantly lower carbonyl levels compared to 3R4F smoke extract at matched nicotine concentrations.
* The aqueous extract of ThS2.2 aerosol exhibited reduced effects on chemotaxis and transendothelial migration compared to 3R4F smoke extract.
* In vitro exposure of hCaECs to ThS2.2 aerosol extract resulted in reduced network perturbation amplitudes and biological impact factors compared to 3R4F smoke extract.
* Exposure of MM6 cells to ThS2.2 aerosol extract resulted in fewer gene expression changes and lower levels of inflammatory marker proteins in conditioned media compared to 3R4F smoke extract.
* The study suggests that ThS2.2 aerosol extract has reduced biological impact on human endothelial cells compared to 3R4F smoke extract.
* The findings support the potential of heat-not-burn tobacco products to reduce the risk for cardiovascular disease compared to combustible cigarettes.

Main Message:
The study provides evidence that ThS2.2 aerosol extract has reduced biological impact on human endothelial cells compared to 3R4F smoke extract. The findings support the potential of heat-not-burn tobacco products to reduce the risk for cardiovascular disease compared to combustible cigarettes, highlighting the importance of developing and regulating modified risk tobacco products that are less harmful than traditional cigarettes.

Poussin, Carine, alexandra Laurent, Manuel C. Peitsch, Julia hoeng, and hector De Leon. “Systems Toxicology-Based assessment of the Candidate Modified Risk Tobacco Product ThS2.2 for the adhesion of Monocytic Cells to human Coronary arterial Endothelial Cells.” Toxicology 339 (January 2016): 73–86. https://doi.org/10.1016/j.tox.2015.11.007.