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The Effects of Prenatal Thirdhand E-cigarette Exposure on Platelets

产前三手电子烟暴露对血小板的影响

基本信息

批准号：
10759130
负责人：
Fadi T Khasawneh
金额：
$ 2.6万
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：
2023
资助国家：
美国
起止时间：
2023-05-01 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10759130
关键词：
Address Animal Diseases Animal Model Biochemical Markers Biology Blood Blood Platelets C-reactive protein Cardiovascular Diseases Cardiovascular system Cigarette Critical Thinking Data Deposition Development Disease Electronic cigarette Electronics Elements Exposure to Foundations Funding Future Gender Goals Health Hemostatic function Home Human Hyperactivity Ingestion Inhalation Laboratories Light Mediating Mentors Minority Nature Pathogenesis Persons Phenotype Plasma Platelet Activation Platelet Count measurement Play Policies Prevention Process Publishing Risk Role Safety Scientist Skin Absorption Smoke Smoking Societies Surface System Testing Therapeutic Thrombosis Time Tobacco Tobacco smoke Toxic effect Training Vulnerable Populations Writing cardiovascular health chemical reaction clinically relevant combustible cigarette design electronic hookah evidence base experimental study exposed human population exposure route in utero novel platelet function pre-doctoral prenatal prenatal exposure research study response sex skills smoking cessation thirdhand smoke thrombogenesis tobacco products toxicant

项目摘要

While smoking has been on the decline, Electronic Delivery Systems (ENDS) usage has been on the rise; especially in vulnerable populations. Furthermore, even though the contribution of in utero third-hand smoke (THS) and e-cigarettes to the pathogenesis of thrombotic diseases have recently been documented, the involvement of prenatal third-hand e-hookah (another form of ENDS) 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 prenatal thirdhand e-hookah, in the context of thrombotic disease and platelet biology, and in a sex-specific manner. These studies are of paramount significance given the “perceived safety” of e-hookahs. The Aims of this proposal are: Aim 1. Investigate the impact of prenatal thirdhand e-hookah exposure on platelet-dependent disease states. While there is compelling evidence that e-cigarettes and in utero thrdhand smoke from traditional cigarettes (THS) do exert negative health effects, the impact of prenatal thirdhand e-hookah on platelet- dependent diseases is still unknown. To address this issue, the consequences of prenatal thirdhand e-hookah exposure on normal hemostasis and platelet counts will be determined. Subsequent studies will examine whether it participates in the development of thrombosis-based disease, and exerts effects on a plasma “marker” of thrombosis. Notably, experiments will be designed in a manner that addresses the role of sex in mediating the “platelet”-dependent negative effects of prenatal thirdhand e-hookah. Aim 2. Investigate the mechanism by which prenatal thirdhand e-hookah exposure modulates platelet function. Even though published data indicate that in utero THS and e-cigarettes modulate platelet activation, whether prenatal thirdhand e-hookah produces similar effects (i.e., the mechanism by which it modulates platelet function) remains to be investigated. Thus, the overall goal of the mechanistic experiments proposed in this section is to determine the impact of prenatal thirdhand e-hookah exposure on the various platelet functional responses (e.g., GPIIb-IIIa activation) and biochemical “markers” of platelet activation. Collectively, these experiments will make significant contributions to the understanding of the consequences of prenatal thirdhand e-hookah/e-hookah on platelet activation and cardiovascular human health, and the mechanism by/through which it exerts these effects, in a sex-specific manner.

虽然吸烟率一直在下降，但电子传输系统 (ENDS) 的使用量却在上升；特别是在弱势群体中。此外，尽管子宫内三手烟的贡献（THS）和电子烟对血栓性疾病发病机制的影响最近已被记录，产前第三手电子水烟（电子烟的另一种形式）与此类疾病过程的关系仍然存在未知。因此，本申请概述了解决基本、机械和产前第三手电子水烟对健康不利影响的临床相关转化方面，血栓性疾病和血小板生物学的背景，并且以性别特异性的方式。这些研究至关重要考虑到电子水烟的“感知安全性”，这一点具有重要意义。该提案的目标是：目标 1. 调查产前接触第三手电子水烟对血小板依赖性疾病的影响州。虽然有令人信服的证据表明电子烟和子宫内三手烟与传统吸烟相比香烟（THS）确实会对健康产生负面影响，产前二手电子水烟对血小板的影响相关疾病尚不清楚。针对这个问题，产前三手电子水烟的后果将确定正常止血和血小板计数的暴露情况。后续研究将检验它是否参与血栓性疾病的发展，并对血浆“标志物”产生影响血栓形成。值得注意的是，实验的设计方式将解决性别在介导产前第三手电子水烟的“血小板”依赖性负面影响。目标 2. 研究产前第三手电子水烟暴露调节血小板的机制功能。尽管已发表的数据表明子宫内 THS 和电子烟可调节血小板活化，产前第三手电子水烟是否产生类似的效果（即它调节血小板的机制）的功能）还有待研究。因此，本文提出的机械实验的总体目标该部分旨在确定产前第三手电子水烟暴露对各种血小板功能的影响反应（例如 GPIIb-IIIa 激活）和血小板激活的生化“标记”。总的来说，这些实验将为理解产前第三手电子水烟/电子水烟对血小板活化和心血管的影响人类健康，以及它以特定性别的方式发挥这些影响的机制。