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.

尽管吸烟一直在下降，但电子烟的使用量仍在上升。特别是在脆弱的情况下 人群。此外，即使子宫三烟（THS）和电子烟的贡献 最近已经记录了血栓性疾病的发病机理 在这种疾病过程中的电子烟（IUTHEC）仍然未知。因此，本申请 概述了针对基本，机械和临床上与临床相关的翻译方面的研究 在血栓性疾病和血小板生物学的背景下以及在设备，E-中 液体和性别特定的方式。鉴于电子的“感知安全性”，这些研究至关重要 香烟将使用新颖/新的Iuthec曝光模型进行。该提案的目的是： 目标1。研究Iuthec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，电子烟和子宫里确实会产生负面影响，这是Iuthec的影响 在血小板依赖性疾病上仍然未知。为了解决这个问题，Iuthec暴露的后果 将确定正常止血和血小板计数。随后的研究将检查Iuthec是否 参与基于血栓形成的疾病的发展。最后，Iuthec对等离子体的影响 还将确定血栓形成的“标记”。值得注意的是，实验将以某种方式进行设计 解决了该设备的作用，以及电子液体在介导Iuthec的“血小板”依赖性负面影响中的作用。 此外，初步数据确实首次显示了Iuthec，在子宫和电子烟中 增加血栓性心血管疾病的风险。 AIM 2。研究Iuthec暴露调节血小板功能的机制。虽然 已发布的数据表明，在子宫内和电子烟中调节血小板激活，是否Iuthec是否 产生相似的效果（即调节血小板功能的机制）仍有待研究。 这就是本节提出的机械实验的总体目标是确定 对各种血小板功能响应（例如GPIIB-IIIA激活）的IUTHEC暴露，血栓烷A2 水平，血小板激活的生化“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/电子烟的后果对血小板激活和心血管人类健康以及 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。