The Effects of Prenatal Thirdhand E-cigarette Exposure on Platelets

虽然吸烟人数一直在下降，但电子传递系统的使用一直在上升; 特别是在弱势群体中。此外，即使子宫内三手烟的贡献 (THS)和电子烟的血栓性疾病的发病机制最近有记录， 产前第三手电子水烟（另一种形式的ENDS）参与这些疾病的过程仍然存在 未知因此，本申请概述了解决基本的、机械的和非机械的问题的研究。 产前三手电子水烟的不良健康影响的临床相关翻译方面， 血栓性疾病和血小板生物学的背景下，并在性别特异性的方式。这些研究至关重要 考虑到电子水烟袋的“安全感”，这一点很重要。这项建议的目的是： 目标1.调查产前三手电子水烟暴露对血小板依赖性疾病的影响 states.虽然有令人信服的证据表明，电子烟和子宫内的传统吸烟方式 香烟（THS）确实对健康产生负面影响，产前三手电子水烟对血小板的影响， 依赖性疾病仍然未知。为了解决这个问题，产前三手电子水烟的后果 将确定正常止血和血小板计数的暴露量。后续研究将探讨 它是否参与了基于血栓形成的疾病的发展，并对血浆“标记物”产生影响， 血栓形成值得注意的是，实验的设计方式将解决性别在调解 “血小板”依赖的负面影响产前三手电子水烟。 目标二。研究产前三手电子水烟暴露调节血小板的机制 功能尽管已发表的数据表明，在子宫内THS和电子烟调节血小板活化， 产前三手电子水烟是否产生类似的效果（即，它调节血小板的机制 功能）仍有待研究。因此，本文提出的机械实验的总体目标是： 部分是为了确定产前三手电子水烟暴露对各种血小板功能的影响， 响应（例如，GPIIb-IIIa活化）和血小板活化的生化“标志物”。 总的来说，这些实验将对理解 产前三手电子水烟/电子水烟对血小板活化和心血管疾病的影响 人类健康，以及它以性别特有的方式发挥这些影响的机制。

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.