The Impact of Third-Hand E#Cigarette Exposure on Platelet Function and Thrombogenesis

三手电子的影响

• 批准号: 10055289
• 负责人: Fatima Z. Alshbool
• 金额: $ 7.58万
• 依托单位: TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-18 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10055289
• 关键词: Address; Agonist; Air; Animal Diseases; Animal Model; Awareness; Biochemical; Biochemical Markers; Biology; Blood Coagulation Factor; Blood Platelets; Cardiovascular Diseases; Cardiovascular system; Cigarette; Data; Dependence; Development; Devices; Disease; Dose; Electronic cigarette; Elements; Exposure to; Foundations; Future; Generations; Goals; Hand; Health; Hemostatic function; Human; Integrins; Investigation; Life; Mediating; Modeling; Mus; Nature; Pathogenesis; Pharmacology; Phenotype; Physiological; Plasma; Platelet Activation; Platelet Count measurement; Platelet aggregation; Play; Policies; Prevention; Process; Public Health; Publishing; Research Design; Risk; Role; Safety; Shapes; Smoke; Smoking; Societies; Stimulus; Therapeutic; Thrombin; Thrombosis; Thromboxane A2; Time; Tobacco; Tobacco Dependence; Tobacco use; Vulnerable Populations; base; cardiovascular disorder risk; cardiovascular health; clinically relevant; design; electronic cigarette use; electronic liquid; evidence base; experimental study; novel; platelet function; receptor; response; sex; thirdhand smoke; thrombogenesis; tobacco control; virtual

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 third-hand smoke (THS) and- more recently- e- cigarettes to the pathogenesis of thrombotic diseases was documented, the involvement of third-hand e- cigarettes (THEC) 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 THEC, 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 THEC exposure model. The Aims of our proposal are: Aim 1. Investigate the impact of THEC exposure on platelet-dependent disease states. While there is compelling evidence that e-cigarettes do exert negative health effects, the impact of THEC on platelet-dependent diseases is still unknown. To address this issue, we will determine the consequences of THEC exposure on normal hemostasis and platelet counts. Subsequent studies will examine whether THEC participates in the development of thrombosis-based disease. Finally, we will determine the effects of THEC on plasma “markers” of thrombosis. Notably, our 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 THEC. Furthermore, our preliminary data does show, for the first time, that THEC, THS and e-cigarettes increase the risk of thrombotic cardiovascular disease. Aim 2. Investigate the mechanism by which THEC exposure modulates platelet function. Even though our published data indicated that THS and e-cigarettes modulate platelet activation, whether THEC produces similar effects (i.e., the mechanism by which it modulates platelet function) remains to be investigated. Thus, the overall goal of the experiments proposed in this section is to determine the impact of THEC exposure on the various platelet functional responses (e.g., GPIIb-IIIa activation), thromboxane A2 levels, and on biochemical “markers” of platelet activation. It is noteworthy that our preliminary data shows that THEC does enhance platelet aggregation and secretion. Collectively, these experiments will make significant contributions to our understanding of the consequences of THEC/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.

尽管吸烟一直在下降，但电子烟的使用量一直在上升。特别是在脆弱的情况下 人群。此外，即使第三烟（THS）和 - 最近的E-的贡献 记录了血栓性疾病发病机理的香烟，第三手E-的参与 在这种疾病过程中的香烟（Thec）仍然未知。因此，本申请概述了 解决不良健康的基本，机械和临床转化方面的研究 Thec的影响，在血栓性疾病和血小板生物学的背景下，以及在设备，电子液体和性别中 具体方式。考虑到电子烟的“感知安全性”，这些研究至关重要，并且 将使用新颖/新的THEC暴露模型进行。我们提案的目的是： 目标1。研究THEC暴露对血小板依赖性疾病状态的影响。而有 令人信服的证据表明电子烟会产生负面的健康影响，THEC对血小板依赖性的影响 疾病仍然未知。为了解决这个问题，我们将确定THEC暴露对 正常止血和血小板计数。随后的研究将检查THEC是否参与 基于血栓形成的疾病的发展。最后，我们将确定THEC对等离子体“标记”的影响 血栓形成。值得注意的是，我们的实验将以解决设备角色的方式进行设计，并且 电子液体介导Thec的“血小板”依赖性负面影响。此外，我们的初步数据确实 首次表明Thec，THS和电子烟会增加血栓性心血管疾病的风险。 AIM 2。研究THEC暴露调节血小板功能的机制。即使我们 已发布的数据表明，THS和电子烟调节血小板激活，Thec是否产生相似的 效应（即调节血小板功能的机制）仍有待研究。那，总体 本节提出的实验的目标是确定THEC暴露对各种的影响 血小板功能反应（例如GPIIB-IIIA激活），血栓烷A2水平以及生化“标记” 血小板激活。值得注意的是，我们的初步数据表明THEC确实增强了血小板 聚集和分泌。 总的来说，这些实验将为我们的理解做出重大贡献 Thec/电子烟在血小板激活和心血管人类健康中的后果，以及 通过/通过设备，电子液体和性别特异性方式执行这些效果的机制。