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

虽然吸烟一直在减少，但电子烟的使用量一直在上升，即使在COVID19期间也是如此 大流行。此外，尽管传统吸烟在血栓形成机制中的作用 虽然电子烟在这些疾病中的作用是有据可查的，但电子烟在这些疾病过程中的参与情况仍不清楚。 因此，本申请概述了涉及基础、机制和临床的研究。 电子烟的不利健康影响的相关翻译方面，电子烟是一种日益流行的 烟草，在血小板生物学、血栓性疾病和性的背景下，以及在设备和电子液体特定的情况下 举止。研究还建议以类似的方式调查电子烟背后的有毒物质 效果。鉴于电子烟的“感知安全”，这些研究具有极其重要的意义。的目标是 这项建议包括： 目的1.研究电子烟暴露对血小板依赖性疾病状态的影响。在那里的时候 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的影响 疾病仍然是未知的。为了解决这些问题，接触电子烟对正常 止血将以剂量和时间依赖的方式确定。后续研究将检查 电子烟是否参与血栓性疾病的发展。最后，实验设计在 一种方式，解决了设备和电子烟效果中的电子液体的作用，性行为是一种生物 变量。 目的2.探讨电子烟调节血小板功能的机制。即使是在 初步数据表明，电子烟可以调节止血，止血的机制是电子烟调节的。 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、生化/血浆的影响 血栓形成的“标志物”，对PGI2的机制抵抗，以及这种影响是否由受体介导。 最后，建议进行研究以确定电子烟是否调节血小板miRNome。 目的3.定义对血小板依赖性疾病和功能有显著影响的电子烟毒物。而当 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，但没有什么是 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 毒物，单独或联合使用，对血小板功能和相关疾病的影响将被调查。 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人类健康的影响 通过/通过它们以剂量、时间、装置、电子液体的方式发挥这些作用的机制和毒物 在性的背景下，具体的方式。

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.