The Effects of Prenatal Thirdhand E-cigarette Exposure on Platelets

虽然吸烟一直在减少，但电子烟的使用量却在上升；特别是在弱势群体中 人口。此外，尽管宫内三手烟(THS)和电子烟对 血栓性疾病的发病机制最近已有文献记载，涉及子宫内第三只手 电子烟(IUTHEC)在这种疾病过程中的作用尚不清楚。因此，本申请 概述了涉及基础、机械性和临床相关的翻译方面的研究 在血栓性疾病和血小板生物学的背景下，以及在一种设备中，IUTHEC对健康的不利影响-，e- 以液体和性别特有的方式。鉴于电子邮件的“感知安全”，这些研究具有重要意义。 将使用一种新的/新的IUTHEC暴露模式进行。这项建议的目的是： 目的1.研究IUTHEC暴露对血小板依赖性疾病状态的影响。趁有机会 令人信服的证据表明，电子烟和宫内THS确实会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尚不清楚。为了解决这个问题，IUTHEC暴露的后果 对正常止血和血小板计数将进行测定。后续研究将检查IUTHEC是否 参与血栓性疾病的发展。最后，IUTHEC对血浆的影响 血栓形成的“标志物”也将被确定。值得注意的是，实验将以这样的方式设计 阐述了该装置和电子液体在调节IUTHEC的“血小板”依赖的负面效应中的作用。 此外，初步数据首次显示，IUTHEC、宫内THS和电子烟 增加血栓性心血管疾病的风险。 目的2.探讨IUTHEC暴露对血小板功能的调节机制。即使 已发表的数据表明，在子宫内，THS和电子烟调节血小板激活，无论IUTHEC 产生类似的作用(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(如GPIIb-IIIa激活)、血栓素A2的影响 以及评估其他血细胞的贡献(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心血管人类健康的影响 通过/通过它以设备、电子液体和性别特定的方式施加这些影响的机制。

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.