Investigation of the Impact of in Utero Thirdhand E-Cigarette Exposure on Platelet Function

Cardiovascular disease (CVD) is the leading cause of death worldwide, with many deaths being due to heart attacks and stroke. To this end, platelets are key players in maintaining and regulating “hemostasis” in the cardiovascular system. However, a disruption in the platelet function (hyperactivity) can promote the genesis of occlusive (thrombosis-based) CVD. Though there are many known risk factors for CVD, the number one preventable risk factor is exposure to tobacco or tobacco related products. Interestingly, the use of emerging tobacco products, specifically e-cigarettes (e-cigs) has been on the rise, achieving unprecedented levels, due to the misconception that they are a safe(r) alternative to traditional cigarette smoking, especially amongst pregnant women or women of childbearing age. Therefore, there has been efforts- including by our laboratory- to characterize the negative effects of smoking on the CV system. To this end, we have previously shown that direct exposure to e-cigs increases the risk of occlusive CVD. However, the effects of indirect exposure to e-cigs, namely thirdhand exposure, which is formed from toxicants “produced” by e-cig vapor that accumulate on surfaces such as upholstery, curtains, car seats, carpet etc., are still unknown, including under in utero settings. To this end, the present studies aim to characterize the impact that in utero thirdhand e-cig (IUTHEC) exposure exerts on platelet function and the CV system and examine the mechanism of these effects. Utilizing a custom e-cig vape system mice were housed with clean air or e-cig-exposed material for one week prior to mating and for the duration of their pregnancy. Using this approach to mimic a real life exposure scenario, our preliminary results indicate that IUTHEC exposed pups exhibited a shortened bleeding and thrombus occlusion times, in two widely used hemostasis and thrombosis models. In terms of the mechanism of this prothrombotic phenotype, it was found that platelet aggregation, as well as dense and alpha granule secretion were potentiated in the IUTHEC exposed mice in response to agonist stimulation. Furthermore, integrin activation and phosphatidylserine exposure, additional markers of platelet function, were also found to be enhanced. These data together demonstrate for the first time that IUTHEC increases the risk of thrombotic CVD in part via modulation of platelet activation. Moreover, our findings highlight the negative health effects of exposure to IUTHEC, which is an underappreciated threat to human health.