Exposure of Mice to Thirdhand Smoke Modulates In Vitro and In Vivo Platelet Responses

Abstract

Smoking is a risk factor for a variety of deleterious conditions, such as cancer, respiratory disease and cardiovascular disease. Thrombosis is an important and common aspect of several cardiovascular disease states, whose risk is known to be increased by both first- and secondhand smoke. More recently, the residual cigarette smoke that persists after someone has smoked (referred to as thirdhand smoke or THS) has been gaining more attention, since it has been shown that it also negatively affects health. Indeed, we have previously shown that 6-month exposure to THS increases the risk of thrombogenesis. However, neither the time-dependence of THS-induced thrombus formation, nor its sex dependence have been investigated. Thus, in the present study, we investigated these issues in the context of a shorter exposure to THS, specifically 3 months, in male and female mice. We show that the platelets from 3-month THS-exposed mice exhibited enhanced activation by agonists. Moreover, we also show that mice of both sexes exposed to THS have decreased tail bleeding as well as decreased thrombus occlusion time. In terms of the role of sex, intersex disparities in thrombus development and hemostasis as well as in platelet aggregation were, interestingly, observed. Together, our findings show that exposing mice to THS for 3 months is sufficient to predispose them to thrombosis; which seems to be driven, at least in part, by an increased activity in platelets, and that it does not manifest equally in both sexes.

Investigation of the impact of thirdhand e-cigarette exposure on platelet function: A pre-clinical study

“…These data indicate that the THEC-exposed platelets are in a hyperactive state in response to agonist stimulation, suggesting that individuals exposed to this form of smoke would be at an increased risk for CVD. While these effects appear to be consistent with what we have seen with THS 7,15 , future studies will focus on directly comparing the effects of THEC and THS.…”

“…In order to mimic real-life exposure scenarios, the following THEC exposure protocol was developed and employed in part, based on the previously described THS protocol 7 . Household materials were exposed to EC vapor utilizing an e-vapeTM vapor inhalation system (La Jolla Alcohol Research, Inc).…”

“…To evaluate the hemostatic function of platelets, the tail bleeding assay was performed on both THEC and CA-exposed C57BL/6 mice, as previously described 7 . Measuring from the tip of the tail, a 5 mm segment was transected with a blade while the mice were under isoflurane anesthesia, and their temperature was monitored and maintained at 37 o C with a homeothermic blanket.…”

“…Thus, these devices leave THEC residues that get embedded and accumulate on surfaces such as, carpets, couches, curtains, clothes, etc., whereby susceptible individuals unknowingly get exposed to 13,14 . Even though we have established a link between THS, including that which is in utero and occlusive CVD 7,15 , nothing is known in the context of THEC. Taken together, it is our aim to characterize the impact THEC exposure has on platelet function and thrombogenesis, using animal models.…”

“…This form of exposure -which is identified as thirdhand smoke (THS) -has also been found to be associated with a negative health impact. For example, THS -was shown to impair wound healing 6 and enhance the risk of thrombosis 7 .…”