The Effects of Prenatal Thirdhand E-cigarette Exposure on Platelets

虽然吸烟一直在下降，但电子烟的使用一直在上升;特别是在弱势群体中， 人口。此外，即使子宫内三手烟（THS）和电子烟对 血栓性疾病的发病机制最近已被证实，子宫内第三手 电子烟（IUTHEC）在这种疾病过程中的作用仍然未知。因此，本申请 概述了研究，解决基本的，机械的，和临床相关的翻译方面的 在血栓性疾病和血小板生物学背景下，以及在器械中， 液体和性别特异性的方式。这些研究具有极其重要的意义，因为"感知安全"的电子- 香烟，并将使用新的/新的IUTHEC暴露模型进行。这项建议的目的是： 目标1。研究IUTHEC暴露对血小板依赖性疾病状态的影响。虽然 令人信服的证据表明，电子烟和子宫内THS确实对健康产生负面影响，IUTHEC的影响 对血小板依赖性疾病的影响仍然未知。为了解决这一问题， 将测定正常止血和血小板计数。随后的研究将检查IUTHEC是否 参与血栓形成疾病的发展。最后，研究了IUTHEC对血浆 还将确定血栓形成的"标记物"。值得注意的是，实验将以这样的方式设计， 阐述了器械和电子液体在介导IUTHEC的"血小板"依赖性负面效应中的作用。 此外，初步数据首次显示，IUTHEC，子宫内THS和电子烟 增加血栓性心血管疾病的风险。 目标2.研究IUTHEC暴露调节血小板功能的机制。即使 已发表的数据表明，在子宫内THS和电子烟调节血小板活化，无论是IUTHEC 产生类似的效果（即，其调节血小板功能的机制）仍有待研究。 因此，本节中提出的机械实验的总体目标是确定 IUTHEC暴露对各种血小板功能反应的影响（例如，GPIIb-IIIa激活），血栓素A2 水平、血小板活化的生物化学"标记物"，以及评估其它血细胞的贡献（例如， 中性粒细胞）和血小板表观遗传学改变为IUTHEC表型。 总的来说，这些实验将对理解 IUTHEC/电子烟对血小板活化和人类心血管健康的后果，以及 它以装置、电子液体和性别特异性方式发挥这些作用的机制。

While smoking has been on the decline, e-cigarette 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 in utero third-hand e-cigarettes (IUTHEC) 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 IUTHEC, in the context of thrombotic disease and platelet biology, and in a device-, e- liquid-, and sex-specific manner. These studies are of paramount significance given the “perceived safety” of e- cigarettes, and will be conducted using a novel/new IUTHEC exposure model. The Aims of this proposal are: Aim 1. Investigate the impact of IUTHEC exposure on platelet-dependent disease states. While there is compelling evidence that e-cigarettes and in utero THS do exert negative health effects, the impact of IUTHEC on platelet-dependent diseases is still unknown. To address this issue, the consequences of IUTHEC exposure on normal hemostasis and platelet counts will be determined. Subsequent studies will examine whether IUTHEC participates in the development of thrombosis-based disease. Finally, the effects of IUTHEC on plasma “markers” of thrombosis will also be determined. Notably, experiments will be designed in a manner that addresses the role of the device, and e-liquid in mediating the “platelet”-dependent negative effects of IUTHEC. Furthermore, the preliminary data does show, for the first time, that IUTHEC, in utero THS and e-cigarettes increase the risk of thrombotic cardiovascular disease. Aim 2. Investigate the mechanism by which IUTHEC exposure modulates platelet function. Even though published data indicate that in utero THS and e-cigarettes modulate platelet activation, whether IUTHEC 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 IUTHEC exposure on the various platelet functional responses (e.g., GPIIb-IIIa activation), thromboxane A2 levels, biochemical “markers” of platelet activation, as well as assess the contribution of other blood cells (e.g., neutrophils) and alterations in the platelet epigenetics to the IUTHEC phenotype. Collectively, these experiments will make significant contributions to the understanding of the consequences of IUTHEC/e-cigarettes on platelet activation and cardiovascular human health, and the mechanism by/through which it exerts these effects, in a device-, e-liquid-, and sex-specific manner.