The Impact of In Utero E-Cigarette Exposure on Platelet Function and Thrombogenesis

子宫内电子烟暴露对血小板功能和血栓形成的影响

• 批准号: 10640062
• 负责人: Fatima Z. Alshbool
• 金额: $ 18.94万
• 依托单位: TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-08 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10640062
• 关键词: Address; Adult; Affect; Agonist; Animal Diseases; Animal Model; Anti-Inflammatory Agents; Automobile Driving; Awareness; Biochemical Markers; Biology; Blood Coagulation Factor; Blood Platelets; Cardiovascular Diseases; Cardiovascular system; DNA Methylation; Data; Development; Disease; Dose; Electronic cigarette; Elements; Epigenetic Process; Exposure to; Female; Female of child bearing age; Foundations; Gender; Goals; Health; Hemostatic function; Human; Mediating; MicroRNAs; Modeling; Morbidity - disease rate; Mus; Nature; Pathogenesis; Phenotype; Physiological; Plasma; Platelet Activation; Play; Policies; Pregnant Women; Prevention; Process; Public Health; Publishing; Risk; Role; Safety; Shapes; Smoke; Smoking; Societies; Stimulus; Therapeutic; Thrombin; Thrombosis; Thrombus; Time; Tobacco; Tobacco Dependence; Tobacco smoking behavior; Tobacco use; Vulnerable Populations; cardiovascular disorder risk; cardiovascular health; clinically relevant; cytokine; design; developmental plasticity; electronic cigarette use; electronic liquid; evidence base; experimental study; in utero; mortality; novel; platelet function; pregnant; prenatal exposure; receptor; response; sex; thrombogenesis; tobacco control; tobacco exposure; virtual

While smoking has been on the decline, e-cigarette usage has been on the rise; especially in vulnerable populations, including pregnant women, who switch to e-cigarettes due to misperceptions regarding their safety. Furthermore, even though the contribution of traditional smoking to the pathogenesis of thrombotic diseases is well documented, the involvement of e-cigarettes in such disease processes remains unknown. Consequently, the present application outlines studies that address fundamental, mechanistic, epigenetic and clinically-relevant translational aspects of the adverse-health effects of in utero exposure to e-cigarettes, an increasingly popular form of tobacco, in the context of thrombotic disease and platelet biology, and in an 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 whole body exposure model. The Aims of this proposal are: Aim 1. Investigate the impact of in utero e-cigarette exposure on platelet-dependent disease states. While there is compelling evidence that e-cigarettes do exert negative health effects, and that in utero exposure to tobacco contributes to thrombogenesis, whether e-cigarettes are associated with an increased risk of thrombotic diseases is yet to be determined. To address this issue, the consequences of in utero e- cigarette exposure on normal hemostasis and whether it participates in the development of thrombotic diseases will be determined. Subsequent studies will assess the impact of in utero e-cigarettes on clotting factors. Aim 2. Investigate the mechanism by which in utero e-cigarette exposure modulates platelet function. It is noteworthy that published data shows that e-cigarettes do enhance platelet function (e.g., aggregation) in adults. Nonetheless, it remains to be determined if in utero e-cigarettes produce similar effects or not. Thus, the overall goal of the experiments proposed in this section is to determine the mechanism and impact of in utero e-cigarette exposure on the various platelet functional responses, specific biochemical markers of platelet activation, pro- and anti-inflammatory, as well as on the platelet epigenetics. Collectively, these experiments will make major contributions to understanding the consequences of in utero exposure to e-cigarettes on platelet activation and cardiovascular human health, its epigenetics, and the mechanism by/through which they exerts these effects, in an e-liquid- and sex- specific manner.

虽然吸烟一直在下降，但电子烟的使用一直在上升;特别是在弱势群体中， 包括孕妇在内的人群由于对电子烟安全性的误解而转向电子烟。 此外，即使传统吸烟对血栓性疾病发病机制的贡献是有限的， 尽管有充分的证据证明，电子烟与此类疾病过程的关系仍然未知。因此，委员会认为， 本申请概述了针对基础、机制、表观遗传和临床相关的研究， 在子宫内暴露于电子烟的不良健康影响的翻译方面，一个越来越受欢迎的 烟草形式，在血栓性疾病和血小板生物学的背景下，以及在电子液体和性别特异性 方式考虑到电子烟的“感知安全性”，这些研究具有至关重要的意义， 使用新的/新的全身暴露模型进行。这项建议的目的是： 目标1.研究宫内电子烟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，电子烟确实会对健康产生负面影响， 烟草有助于血栓形成，电子烟是否与风险增加有关 血栓性疾病的发病率尚待确定。为了解决这个问题，在子宫内的后果- 香烟暴露对正常止血的影响及其是否参与血栓形成的发展 疾病将被确定。随后的研究将评估子宫内电子烟对凝血的影响 因素 目标2.研究子宫内电子烟暴露调节血小板功能的机制。它 值得注意的是公开的数据显示电子烟确实增强血小板功能（例如，聚合） 成年人了尽管如此，子宫内的电子烟是否会产生类似的效果仍有待确定。因此，在本发明中， 本节所提出的实验的总体目标是确定这种影响的机制和影响， 子宫内电子烟暴露对各种血小板功能反应的影响， 血小板活化，促炎和抗炎，以及对血小板表观遗传学的影响。 总的来说，这些实验将为理解 在子宫内暴露于电子烟对血小板活化和心血管人类健康，其 表观遗传学，以及它们发挥这些作用的机制，在一个电子液体和性别- 具体方式。