The Impact of In Utero E-Cigarette Exposure on Platelet Function and Thrombogenesis

虽然吸烟率一直在下降，但电子烟的使用量却在上升。尤其是在弱势群体 由于对电子烟安全性的误解，包括孕妇在内的人群转而使用电子烟。 此外，尽管传统吸烟对血栓性疾病发病机制的贡献是 有据可查，但电子烟与此类疾病过程的关系仍然未知。因此， 本申请概述了涉及基础、机制、表观遗传和临床相关的研究 子宫内接触电子烟对健康的不利影响的转化方面，电子烟是一种越来越受欢迎的电子烟 烟草形式，在血栓性疾病和血小板生物学的背景下，以及在电子液体和性别特定的情况下 方式。鉴于电子烟的“感知安全性”，这些研究具有至关重要的意义，并将 使用新颖/新的全身暴露模型进行。该提案的目标是： 目标 1. 调查子宫内电子烟暴露对血小板依赖性疾病状态的影响。同时 有令人信服的证据表明电子烟确实会对健康产生负面影响，并且在子宫内暴露 烟草会导致血栓形成，电子烟是否会增加风险 血栓性疾病的发病率尚未确定。为了解决这个问题，宫内电子的后果 香烟暴露对正常止血的影响及其是否参与血栓形成 疾病将被确定。后续研究将评估子宫内电子烟对凝血的影响 因素。 目标 2. 研究子宫内电子烟暴露调节血小板功能的机制。它 值得注意的是，已发表的数据表明，电子烟确实增强了血小板功能（例如聚集） 成人。尽管如此，子宫内电子烟是否会产生类似的效果仍有待确定。因此， 本节提出的实验的总体目标是确定 in 的机制和影响 子宫内电子烟暴露对各种血小板功能反应、特定生化标志物的影响 血小板活化、促炎和抗炎以及血小板表观遗传学。 总的来说，这些实验将为理解后果做出重大贡献 子宫内接触电子烟对血小板活化和心血管人类健康的影响 表观遗传学，以及它们在电子液体和性别中发挥这些作用的机制 具体方式。

While smoking has been on the decline, e-cigarette usage has been on the rise; especially in vulnerable populations, including pregnant women, who switch to e-cigarettes due to misperceptions regarding their safety. Furthermore, even though the contribution of traditional smoking to the pathogenesis of thrombotic diseases is well documented, the involvement of e-cigarettes in such disease processes remains unknown. Consequently, the present application outlines studies that address fundamental, mechanistic, epigenetic and clinically-relevant translational aspects of the adverse-health effects of in utero exposure to e-cigarettes, an increasingly popular form of tobacco, in the context of thrombotic disease and platelet biology, and in an 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 whole body exposure model. The Aims of this proposal are: Aim 1. Investigate the impact of in utero e-cigarette exposure on platelet-dependent disease states. While there is compelling evidence that e-cigarettes do exert negative health effects, and that in utero exposure to tobacco contributes to thrombogenesis, whether e-cigarettes are associated with an increased risk of thrombotic diseases is yet to be determined. To address this issue, the consequences of in utero e- cigarette exposure on normal hemostasis and whether it participates in the development of thrombotic diseases will be determined. Subsequent studies will assess the impact of in utero e-cigarettes on clotting factors. Aim 2. Investigate the mechanism by which in utero e-cigarette exposure modulates platelet function. It is noteworthy that published data shows that e-cigarettes do enhance platelet function (e.g., aggregation) in adults. Nonetheless, it remains to be determined if in utero e-cigarettes produce similar effects or not. Thus, the overall goal of the experiments proposed in this section is to determine the mechanism and impact of in utero e-cigarette exposure on the various platelet functional responses, specific biochemical markers of platelet activation, pro- and anti-inflammatory, as well as on the platelet epigenetics. Collectively, these experiments will make major contributions to understanding the consequences of in utero exposure to e-cigarettes on platelet activation and cardiovascular human health, its epigenetics, and the mechanism by/through which they exerts these effects, in an e-liquid- and sex- specific manner.