Investigate the mechanism and impact of E-cigarettes on platelet function and thrombogenesis

虽然吸烟一直在下降，但电子烟的使用一直在上升，即使在COVID 19期间也是如此。 流行病此外，即使传统吸烟对血栓性疾病发病机制的贡献 虽然电子烟对疾病的影响有很好的记录，但电子烟在这种疾病过程中的参与仍然是未知的。 因此，本申请概述了解决基本的、机械的和临床上的问题的研究。 电子烟的不良健康影响的相关翻译方面，电子烟是一种越来越受欢迎的吸烟形式， 烟草，在血小板生物学，血栓性疾病和性别的背景下，并在设备，和电子液体特定 方式研究还建议以类似的方式调查电子烟的有毒物质 方面的影响.考虑到电子烟的“感知安全性”，这些研究具有至关重要的意义。的目的 这些建议是： 目标1.研究电子烟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，电子烟确实会对健康产生负面影响，它们对血小板依赖性 疾病仍然未知。为了解决这些问题，电子烟暴露对正常人的后果 将以剂量和时间依赖性方式测定止血作用。后续研究将探讨 电子烟是否参与血栓形成疾病的发展。最后，设计了实验， 一种解决设备的作用的方式，以及电子烟中的电子液体效果，以性作为生物学 变量 目标二。研究电子烟调节血小板功能的机制。即使 初步数据表明，电子烟调节止血， 血小板功能仍有待研究。因此，本节中提出的实验的总体目标是 为了确定电子烟暴露对各种血小板功能反应的影响， 血栓形成的"标志物"、对PGI2的机械抗性以及效应是否是受体介导的。 最后，提出研究以确定电子烟是否调节血小板miRnome。 目标3：定义对血小板依赖性疾病和功能有潜在影响的电子烟毒物。而 众所周知，电子烟是大量有毒物质的来源，如可替宁和丙烯醛，没有什么是 已知它们对血小板活化/疾病的具体影响。因此，电子烟的效果 将研究毒物单独或组合对血小板功能和相关疾病的影响。 总的来说，这些实验将对理解 电子烟对血小板活化和心血管健康的影响，以及 它们发挥这些作用的机制和毒物，以剂量、时间、装置、电子液体的形式， 具体的方式，在性别方面。

While smoking has been on the decline, e-cigarette usage has been on the rise, even during the COVID19 pandemic. 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, and clinically- relevant translational aspects of the adverse-health effects of e-cigarettes, an increasingly popular form of tobacco, in the context of platelet biology, thrombotic disease and sex, and in a device-, and e-liquid-specific manner. Studies are also proposed to investigate, in a similar fashion, the toxicants that underlie e-cigarette effects. These studies are of paramount significance given the “perceived safety” of e-cigarettes. The Aims of this proposal are: Aim 1. Investigate the impact of e-cigarette exposure on platelet-dependent disease states. While there is compelling evidence that e-cigarettes do exert negative health effects, their impact on platelet-dependent diseases is still unknown. To address these issues, the consequences of e-cigarette exposure on normal hemostasis be will determined, in a dose-, and time-dependent fashion. Subsequent studies will examine whether e-cigarettes participate in the development of thrombosis disease. Finally, experiments are designed in a manner that addresses the role of the device, and e-liquid in e-cigarette effects, with sex as a biological variable. Aim 2. Investigate the mechanism by which e-cigarettes modulate platelet function. Even though the preliminary data indicated that e-cigarettes modulate hemostasis, the mechanism, by which they modulate platelet function remains to be investigated. Thus, the overall goal of the experiments proposed in this section is to determine the impact of e-cigarette exposure on the various platelet functional responses, biochemical/plasma “markers” of thrombosis, the mechanistic resistance to PGI2, and whether the effects are receptor mediated. Finally, studies are proposed to determine if e-cigarettes modulate the platelet miRnome. Aim 3. Define e-cigarettes toxicants with potent impact on platelet-dependent disease and function. While e-cigarettes are known to be source of a large number of toxicants, such as cotinine and acrolein, nothing is known regarding their specific impact on platelet activation/disease. Therefore, the effect of the e-cigarette toxicants, alone or in combination, on platelet function and associated disease will be investigated. Collectively, these experiments will make significant contributions to the understanding of the consequences of e-cigarettes on platelet activation and cardiovascular human health, and the mechanism and toxicants by/through which they exert these effects, in a dose-, time-, device-, e-liquid- specific manner, in the context of sex.