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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.

虽然吸烟人数一直在下降，但电子烟的使用量一直在上升；尤其是弱势群体