Increased Expression of Proatherogenic Proteins in Immune Cell Subtypes in Tobacco Cigarette Smokers But Not in Electronic Cigarette Vapers.

Introduction:
This text reports a study that aimed to understand how oxidative stress, triggered by smoking and vaping, affects specific subsets of immune cells and their contribution to atherogenesis. The study focused on the toll-like receptor 4 (TLR4) in the inflammasome-interleukin (IL)-6 signalling axis in monocyte subtypes and T cells.

Key Points:

* Tobacco cigarette smoking, but not electronic-cigarette vaping, is associated with increased expression of major proteins in the TLR4-inflammasome-IL-6 signalling axis in monocyte subtypes and T cells.
* TLR4 senses oxidative stress in immune cells, and caspase-1 is a key protein of inflammasome activation, while IL-6R is the receptor for IL-6 that drives proatherogenic IL-6 signalling.
* The non-nicotine, pro-oxidant toxicants in tobacco cigarette smoke may instigate increased expression of key proteins in the TLR4-inflammasome-IL-6 axis, contributing to atherogenesis.
* The study design included healthy male and female volunteers between the ages of 21 and 45 years who were chronic (>1 year) tobacco cigarette smokers, electronic cigarette vapers, or nonsmokers.
* The study measured end-tidal CO in ECIG vapers and nonsmokers to confirm none were surreptitiously smoking tobacco cigarettes.
* The study used flow cytometry to determine the expression of TLR4, caspase-1, and IL-6R-a in immune cell subtypes and found increased expression in classical and CD4+ T cells of tobacco cigarette smokers but not in ECIG vapers compared with nonsmokers.
* The study also found that the percent of cells positive for caspase-1 was significantly and strikingly decreased in classical monocytes, CD8+ and CD4+ T cells in ECIG vapers compared with nonsmokers.

Main Message:
The main message of this study is that the non-nicotine, pro-oxidant toxicants in tobacco cigarette smoke appear to instigate increased expression of key proteins in the TLR4-inflammasome-IL-6 axis, contributing to atherogenesis. This suggests that electronic cigarettes may be less likely to promote inflammation, including inflammatory atherosclerosis, compared with tobacco cigarettes, and supports additional investigations into the role of electronic cigarettes as part of a harm reduction strategy for adults addicted to tobacco cigarettes who are unwilling or unable to quit.

Kelesidis T, Zhang Y, Tran E, Sosa G, Middlekauff hR. Increased Expression of Proatherogenic Proteins in Immune Cell Subtypes in Tobacco Cigarette Smokers But Not in Electronic Cigarette Vapers. The Canadian journal of cardiology. 2021;37(8):1175-1180. doi:10.1016/j.cjca.2021.05.006