Platelet activation, adhesion, inflammation, and aggregation potential are altered in the presence of electronic cigarette extracts of variable nicotine concentrations

Abstract

Tobacco smoke extracts prepared from both mainstream and sidestream smoking have been associated with heightened platelet activation, aggregation, adhesion, and inflammation. Conversely, it has been shown that pure nicotine inhibits similar platelet functions. In this work, we 1) evaluated the effects of e-cigarette extracts on platelet activities and 2) elucidated the differences between the nicotine-dependent and non-nicotine dependent (e.g. fine particulate matter or toxic compounds) effects of tobacco and e-cigarette products on platelet activities. To accomplish these goals, platelets from healthy volunteers (n = 50) were exposed to tobacco smoke extracts, e-cigarette vapor extracts, and pure nicotine and changes in platelet activation, adhesion, aggregation, and inflammation were evaluated, using optical aggregation, flow cytometry, and ELISA methods. Interestingly, the exposure of platelets to e-vapor extracts induced a significant up-regulation in the expression of the pro-inflammatory gC1qR and cC1qR and induced a marked increase in the deposition of C3b as compared with traditional tobacco smoke extracts. Similarly, platelet activation, as measured by a prothrombinase based assay, and platelet aggregation were also significantly enhanced after exposure to e-vapor extracts. Finally, platelet adhesion potential toward fibrinogen, von Willebrand factor, and other platelets was also enhanced after exposure to e-cigarette vapor extracts. In the presence of pure nicotine, platelet functions were observed to be inhibited, which further suggests that other constituents of tobacco smoke and electronic vapor can antagonize platelet functions, however, the presence of nicotine in extracts somewhat perpetuated the platelet functional changes in a dose-dependent manner.

Short‐Term E‐Cigarette Exposure Increases the Risk of Thrombogenesis and Enhances Platelet Function in Mice

“…These findings support the notion that e‐cigarettes result in a state of platelet hyperactivity, which underlies, at least in part, the prothrombotic phenotype in the exposed mice. Additionally, these data are consistent with those seen in the e‐cigarette vapor extract–exposed human platelet16 studies, in which several functional responses were enhanced (eg, aggregation). Moreover, our data revealed that the e‐cigarette–exposed platelets are less sensitive to inhibition by PGI 2 , in comparison to those from clean air; which may have also contributed to the thrombosis phenotype in these mice.…”

“…To this end, it was recently shown that treatment with e‐cigarette extracts enhances platelet activation16; whether such effects would manifest under whole‐body e‐cigarette exposure experimental settings is unknown. Thus, we next sought to investigate the effects of e‐cigarette exposure on G‐protein–coupled receptor agonist–induced platelet aggregation.…”

“…It is noteworthy that exposure to some of these toxicants, albeit from traditional tobacco smoking and other sources, was found to be associated with an enhanced platelet activation phenotype 6. Furthermore, while the effects of nicotine on platelet activation/aggregation are still controversial,16, 105, 106, 107, 108 particulate matter109, 110 and acrolein93 were indeed found to enhance platelet function.…”

“…To this end, albeit associated with limitation, this study reported that exposure of platelets to e‐cigarette extracts in vitro enhanced platelet activation16 (eg, aggregation and adhesion). Consequently, findings from this study suggested that e‐cigarettes may potentially increase the risk of thrombosis 16. However, this study neither mimicked real‐life conditions (eg, employed e‐cigarette extracts) nor used an in vivo whole‐body exposure model to investigate the effects of e‐cigarettes on platelets.…”

Electronic cigarettes—A review of the physiological health effects

“…(Bahl et al 2012;Romagna et al 2013;Cervellati et al 2014;Willershausen et al 2014;Scheffler et al 2015aScheffler et al , 2015bSchweitzer et al 2015;Tartell 2015). Hom et al (2016) also reported platelet activation, aggregation, and adhesion under EC vapour extracts in vitro. However, some researchers report no cytotoxicity involved with ECs (Wu et al 2014).…”