Cardiovascular diseases are the major cause of death globally. The most important preventable risk factor is smoking, which applies to ~20% of cardiovascular associated deaths. One strategy for tobacco harm reduction is the development of novel tobacco and nicotine products. Recently, new tobacco products based on heating rather than burning tobacco have been launched. These tobacco heating products (THP) are supposed to have a less potential to provoke diseases from smoking compared to conventional cigarette smoking. So far, there are only very few studies regarding the harmful effects of tobacco heating products and the impact on the cardiovascular system and vascular function still remains uncertain.

Own previous studies revealed an impaired endothelial function after stimulation with conventional cigarette smoke in vitro, displayed by an activation of anti-oxidative and pro inflammatory pathways, increased monocyte-endothelial cell adhesion and reduced wound healing capability of human endothelial cells. In contrast, stimulation with THP clearly showed a delayed onset of these major atherosclerotic key parameters in human endothelial cells. Based on these in vitro findings, we hypothesized that THP provoke less deleterious effects on vascular function compared to conventional cigarettes.
  

Human samples of the internal thoracic artery (ITA) of male patients (60-75 years) undergoing an elective coronary artery bypass grafting (CABG) were used for ex vivo vessel function analysis using a Mulvany myograph, gene expression analyses and histologic studies. First, we analyzed these parameters ITA segments between smokers and non-smokers. To evaluate the impact of different tobacco products, ITA vessel segments were incubated ex vivo with various dosages of 3R4F or THP for 90 min. This was followed by analyses of the vascular function and gene expression.

In this study, patients described as smokers had compared with non-smokers a lower age when undergoing CABG. Our study revealed a decreased maximal potassium (K⁺) and noradrenaline (NA)-depended vasocontraction in smokers compared to non-smokers. However, no differences in vasodilation or histologic parameters (CD45+ staining; intima media ratio) was measurable between the groups. Gene expression data indicated a slightly activation of anti-oxidative (HMOX1;CYP1A1) and pro-inflammatory genes (ICAM1;CCL2) in smokers compared to non-smokers. Ex vivo stimulation of ITA segments with 3R4F resulted in a dose-dependent decreased vasocontraction, whereas THP incubation did not affect the K⁺ and NA induced contraction. 3R4F led also to an impaired SNP-dependent vasodilation at highest concentration, yet no effect of THP on the vasodilation was observable. Surprisingly, expression analysis revealed reduced HMOX1 and ICAM1 mRNA expression by 3R4F and no effects by THP incubation.
 

This study corroborates the well-known pathogenic impact of smoking to the cardiovascular system with an impaired vessel contractility of the ITA in smokers. Treatment with 3R4F, but not with THP, had similar deleterious effects on the vascular function, giving evidence for a less pathological impact of these novel smoking products to the cardiovascular system.