The Effects of Prenatal Thirdhand E-cigarette Exposure on Platelets

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While smoking has been on the decline, Electronic Delivery Systems (ENDS) usage has been on the rise; especially in vulnerable populations. Furthermore, even though the contribution of in utero third-hand smoke (THS) and e-cigarettes to the pathogenesis of thrombotic diseases have recently been documented, the involvement of prenatal third-hand e-hookah (another form of ENDS) in such disease processes remains unknown. Consequently, the present application outlines studies that address fundamental, mechanistic, and clinically-relevant translational aspects of the adverse-health effects of prenatal thirdhand e-hookah, in the context of thrombotic disease and platelet biology, and in a sex-specific manner. These studies are of paramount significance given the “perceived safety” of e-hookahs. The Aims of this proposal are: Aim 1. Investigate the impact of prenatal thirdhand e-hookah exposure on platelet-dependent disease states. While there is compelling evidence that e-cigarettes and in utero thrdhand smoke from traditional cigarettes (THS) do exert negative health effects, the impact of prenatal thirdhand e-hookah on platelet- dependent diseases is still unknown. To address this issue, the consequences of prenatal thirdhand e-hookah exposure on normal hemostasis and platelet counts will be determined. Subsequent studies will examine whether it participates in the development of thrombosis-based disease, and exerts effects on a plasma “marker” of thrombosis. Notably, experiments will be designed in a manner that addresses the role of sex in mediating the “platelet”-dependent negative effects of prenatal thirdhand e-hookah. Aim 2. Investigate the mechanism by which prenatal thirdhand e-hookah exposure modulates platelet function. Even though published data indicate that in utero THS and e-cigarettes modulate platelet activation, whether prenatal thirdhand e-hookah produces similar effects (i.e., the mechanism by which it modulates platelet function) remains to be investigated. Thus, the overall goal of the mechanistic experiments proposed in this section is to determine the impact of prenatal thirdhand e-hookah exposure on the various platelet functional responses (e.g., GPIIb-IIIa activation) and biochemical “markers” of platelet activation. Collectively, these experiments will make significant contributions to the understanding of the consequences of prenatal thirdhand e-hookah/e-hookah on platelet activation and cardiovascular human health, and the mechanism by/through which it exerts these effects, in a sex-specific manner.