Systems toxicology study reveals reduced impact of heated tobacco product aerosol extract relative to cigarette smoke on premature aging and exacerbation effects in aged aortic cells in vitro

Published By  C Poussin, M Van der Toorn, S Scheuner, R Piault, A Kondylis, R Savioz*, R Dulize, D Peric, E Guedj, F Maranzano, C Merg, M Morelli, A L Egesipe, S Johne, S Majeed, C Pak, T Schneider, W Schlage, NV Ivanov, M Peitsch, J Hoeng

Published in Archives of Toxicology    
* This author is not affiliated with PMI.


Aging and smoking are major risk factors for cardiovascular diseases (CVD). Our in vitro study compared, in the context of aging, the efects of the aerosol of Tobacco Heating System 2.2 (THS; an electrically heated tobacco product) and 3R4F reference cigarette smoke (CS) on processes that contribute to vascular pathomechanisms leading to CVD. Young and old human aortic smooth muscle cells (HAoSMC) were exposed to various concentrations of aqueous extracts (AE) from 3R4F CS [0.014–0.22 pufs/mL] or THS aerosol [0.11–1.76 pufs/mL] for 24 h. Key markers were measured by high-content imaging, transcriptomics profling and multianalyte profling. In our study, in vitro aging increased senescence, DNA damage, and infammation and decreased proliferation in the HAoSMCs. At higher concentrations of 3R4F AE, young HAoSMCs behaved similarly to aged cells, while old HAoSMCs showed additional DNA damage and apoptosis efects. At 3R4F AE concentrations with the maximum efect, the THS AE showed no signifcant efect in young or old HAoSMCs. It required an approximately ten-fold higher concentration of THS AE to induce efects similar to those observed with 3R4F. These efects were independent of nicotine, which did not show a signifcant efect on HAoSMCs at any tested concentration. Our results show that 3R4F AE accelerates aging in young HAoSMCs and exacerbates the aging efect in old HAoSMCs in vitro, consistent with CS-related contributions to the risk of CVD. Relative to 3R4F AE, the THS AE showed a signifcantly reduced impact on HAoSMCs, suggesting its lower risk for vascular SMC-associated pathomechanisms leading to CVD.