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

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 由于对电子烟安全性的误解而改用电子烟的人群，包括孕妇。 此外，尽管传统吸烟对血栓性疾病的发病机制的贡献是 有充分的证据表明，电子烟在这种疾病过程中的参与仍不清楚。因此， 本申请概述了涉及基础、机制、表观遗传学和临床相关的研究 在子宫内暴露于电子烟的不利健康影响的翻译方面，一种日益流行的 烟草的形式，在血栓性疾病和血小板生物学的背景下，以及在e-液体和性别特有的情况下 举止。鉴于电子烟的“感知安全”，这些研究具有极其重要的意义，并将 使用新的/新的全身暴露模型进行。这项建议的目的是： 目的1.研究宫内电子烟暴露对血小板依赖性疾病状态的影响。而当 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，而且在子宫内接触电子烟 吸烟会导致血栓形成，电子烟是否会增加风险 血栓性疾病的病因尚未确定。为了解决这个问题，宫内e- 香烟暴露对正常止血及其是否参与血栓形成的影响 疾病将会被确定。后续研究将评估宫内电子烟对凝血的影响 各种因素。 目的2.探讨宫内暴露电子烟对小鼠血小板功能的调节机制。它 值得注意的是，公布的数据显示，电子烟确实增强了体内的血小板功能(例如，聚集)。 成年人。尽管如此，在子宫内电子烟是否会产生类似的效果还有待确定。因此， 本部分中提出的实验的总体目标是确定 子宫电子烟暴露对各种血小板功能反应、特异性生化标志物的影响 血小板活化、促炎和抗炎，以及对血小板表观遗传学的影响。 总而言之，这些实验将对理解 子宫内暴露于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中发挥这些效应的机制--和性-- 具体的方式。

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.