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

三手电子的影响

基本信息

批准号：
10265513
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
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-18 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10265513
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 thrombotic tobacco control virtual

项目摘要

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.

虽然吸烟率一直在下降，但电子烟的使用量却在上升，尤其是在弱势群体中。此外，尽管三手烟（THS）和最近的电子烟的贡献。香烟对血栓性疾病发病机制的记录表明，二手电子产品的参与本申请概述了香烟（THEC）在此类疾病过程中的作用尚不清楚。解决不良健康的基本、机制和临床相关转化方面的研究 THEC 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。将使用新颖/新的 THEC 暴露模型进行我们提案的目标是：目标 1. 研究 THEC 暴露对血小板依赖性疾病状态的影响。令人信服的证据表明电子烟确实会对健康产生负面影响，THEC 对血小板依赖性的影响为了解决这个问题，我们将确定THEC暴露对疾病的影响。正常的止血和血小板计数将检查THEC是否参与。最后，我们将确定 THEC 对血浆“标志物”的影响。值得注意的是，我们的实验将以解决设备的作用的方式设计，并且电子烟油可以调节THEC的“血小板”依赖性负面影响此外，我们的初步数据确实如此。首次表明THEC、THS和电子烟会增加血栓性心血管疾病的风险。目标 2. 研究 THEC 暴露调节血小板功能的机制。已发表的数据表明，THS 和电子烟调节血小板活化，THEC 是否产生类似的作用其影响（即其调节血小板功能的机制）仍有待研究。本节中提出的实验的目的是确定THEC暴露对各种血小板功能反应（例如 GPIIb-IIIa 激活）、血栓素 A2 水平以及生化“标志物” 值得注意的是，我们的初步数据表明 THEC 确实能增强血小板。聚集和分泌。总的来说，这些实验将为我们理解 THEC/电子烟对血小板活化和心血管人类健康的影响，以及它以设备、电子液体和性别特定的方式发挥这些作用的机制。