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

• 批准号: 10892421
• 负责人: Fadi T Khasawneh
• 金额: $ 4.06万
• 依托单位: TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR
• 依托单位国家: 美国
• 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/10892421
• 关键词: Address; Adult; Agonist; Air; Animal Diseases; Animal Model; Automobile Driving; Awareness; Biochemical Markers; Biology; Blood Cells; Blood Coagulation Factor; Blood Platelets; C-reactive protein; Cardiovascular Diseases; Cardiovascular system; DNA Methylation; Data; Development; Devices; Disease; Disease Marker; Dose; Electronic cigarette; Elements; Epigenetic Process; Exposure to; Foundations; Future; Gender; Generations; Goals; Health; Hemostatic function; Human; Investigation; Life; Mediating; MicroRNAs; Modeling; Morbidity - disease rate; Mus; Nature; Pathogenesis; Phenotype; Physiological; Plasma; Platelet Activation; Platelet Count measurement; Play; Policies; Prevention; Process; Public Health; Publishing; Risk; Role; Safety; Shapes; Smoke; Smoking; Societies; Stimulus; Therapeutic; Thrombin; Thrombosis; Thromboxane A2; Thrombus; Time; Tobacco; Tobacco Dependence; Tobacco smoking behavior; Tobacco use; Vulnerable Populations; cardiovascular disorder risk; cardiovascular health; clinically relevant; design; developmental plasticity; electronic cigarette use; electronic liquid; evidence base; experimental study; extracellular; in utero; mortality; neutrophil; novel; platelet function; prenatal; prenatal exposure; receptor; response; sex; thirdhand smoke; thrombogenesis; thrombotic; tobacco control

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 in utero third-hand smoke (THS) and e-cigarettes to the pathogenesis of thrombotic diseases have recently been documented, the involvement of in utero third-hand e-cigarettes (IUTHEC) 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 IUTHEC, 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 IUTHEC exposure model. The Aims of this proposal are: Aim 1. Investigate the impact of IUTHEC exposure on platelet-dependent disease states. While there is compelling evidence that e-cigarettes and in utero THS do exert negative health effects, the impact of IUTHEC on platelet-dependent diseases is still unknown. To address this issue, the consequences of IUTHEC exposure on normal hemostasis and platelet counts will be determined. Subsequent studies will examine whether IUTHEC participates in the development of thrombosis-based disease. Finally, the effects of IUTHEC on plasma “markers” of thrombosis will also be determined. Notably, 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 IUTHEC. Furthermore, the preliminary data does show, for the first time, that IUTHEC, in utero THS and e-cigarettes increase the risk of thrombotic cardiovascular disease. Aim 2. Investigate the mechanism by which IUTHEC exposure modulates platelet function. Even though published data indicate that in utero THS and e-cigarettes modulate platelet activation, whether IUTHEC 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 IUTHEC exposure on the various platelet functional responses (e.g., GPIIb-IIIa activation), thromboxane A2 levels, biochemical “markers” of platelet activation, as well as assess the contribution of other blood cells (e.g., neutrophils) and alterations in the platelet epigenetics to the IUTHEC phenotype. Collectively, these experiments will make significant contributions to the understanding of the consequences of IUTHEC/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，尽管子宫内三手烟（THS）和电子烟对人群的影响。 最近记录了血栓性疾病的发病机制，子宫内第三手参与 电子烟（IUTHEC）在此类疾病过程中的作用尚不清楚，目前的应用。 概述了解决基本、机制和临床相关转化方面的研究 在血栓性疾病和血小板生物学的背景下，以及在设备、电子设备中，IUTHEC 的不良健康影响 考虑到电子产品的“感知安全性”，这些研究具有重要意义。 香烟，并将使用新颖/新的 IUTHEC 暴露模型进行 该提案的目标是： 目标 1. 研究 IUTHEC 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和子宫内 THS 确实会对健康产生负面影响，IUTHEC 的影响 对于血小板依赖性疾病的影响仍然未知。为了解决这个问题，IUTHEC 暴露的后果。 后续研究将确定 IUTHEC 是否对正常止血和血小板计数有影响。 最后，IUTHEC 对血浆的影响。 值得注意的是，还将确定血栓形成的“标志物”。 阐述了该设备和电子液体在调节 IUTHEC 的“血小板”依赖性负面影响中的作用。 此外，初步数据确实首次表明，IUTHEC、子宫内 THS 和电子烟 增加血栓性心血管疾病的风险。 目标 2. 研究 IUTHEC 暴露调节血小板功能的机制。 已发表的数据表明，子宫内 THS 和电子烟调节血小板活化，无论 IUTHEC 产生类似的作用（即其调节血小板功能的机制）仍有待研究。 因此，本节提出的机械实验的总体目标是确定 IUTHEC 暴露于各种血小板功能反应（例如 GPIIb-IIIa 激活）、血栓素 A2 水平、血小板活化的生化“标记”，以及评估其他血细胞的贡献（例如， 中性粒细胞）和血小板表观遗传学对 IUTHEC 表型的改变。 总的来说，这些实验将为理解 IUTHEC/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。