Investigate the mechanism and impact of E-cigarettes on platelet function and thrombogenesis

研究电子烟对血小板功能和血栓形成的机制和影响

• 批准号: 10683785
• 负责人: Fatima Z. Alshbool
• 金额: $ 53.49万
• 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: 2022-09-20 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10683785
• 关键词: Acrolein; Address; Agonist; Animal Diseases; Animal Model; Awareness; Behavior; Biochemical; Biochemical Markers; Biological; Biology; Blood; Blood Coagulation Factor; Blood Platelets; COVID-19 pandemic; Cardiovascular Diseases; Cardiovascular system; Clot retraction; Cotinine; Data; Dependence; Development; Devices; Disease; Dose; Electronic cigarette; Elements; Epoprostenol; Exposure to; Foundations; Goals; Health; Hemostatic function; Human; JUUL; Life; Mediating; Morbidity - disease rate; Mus; Nature; Nicotine; Pathogenesis; Perception; Pharmacology; Physiological; Plasma; Platelet Activation; Play; Policies; Prevention; Process; Public Health; Research Design; Resistance; Risk; Role; Safety; Shapes; Smoking; Source; Stimulus; System; Therapeutic; Thrombosis; Thrombus; Time; Tobacco; Tobacco Industry; Tobacco smoking behavior; Tobacco use; Toxic effect; United States; base; biological systems; cardiovascular disorder risk; cardiovascular health; clinically relevant; design; electronic cigarette use; electronic cigarette user; electronic liquid; evidence base; experimental study; mortality; mouse model; platelet function; receptor; response; sex; thrombogenesis; tobacco control; tobacco toxicant; toxicant; vaping

While smoking has been on the decline, e-cigarette usage has been on the rise, even during the COVID19 pandemic. 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, and clinically- relevant translational aspects of the adverse-health effects of e-cigarettes, an increasingly popular form of tobacco, in the context of platelet biology, thrombotic disease and sex, and in a device-, and e-liquid-specific manner. Studies are also proposed to investigate, in a similar fashion, the toxicants that underlie e-cigarette effects. These studies are of paramount significance given the “perceived safety” of e-cigarettes. The Aims of this proposal are: Aim 1. Investigate the impact of e-cigarette exposure on platelet-dependent disease states. While there is compelling evidence that e-cigarettes do exert negative health effects, their impact on platelet-dependent diseases is still unknown. To address these issues, the consequences of e-cigarette exposure on normal hemostasis be will determined, in a dose-, and time-dependent fashion. Subsequent studies will examine whether e-cigarettes participate in the development of thrombosis disease. Finally, experiments are designed in a manner that addresses the role of the device, and e-liquid in e-cigarette effects, with sex as a biological variable. Aim 2. Investigate the mechanism by which e-cigarettes modulate platelet function. Even though the preliminary data indicated that e-cigarettes modulate hemostasis, the mechanism, by which they modulate platelet function remains to be investigated. Thus, the overall goal of the experiments proposed in this section is to determine the impact of e-cigarette exposure on the various platelet functional responses, biochemical/plasma “markers” of thrombosis, the mechanistic resistance to PGI2, and whether the effects are receptor mediated. Finally, studies are proposed to determine if e-cigarettes modulate the platelet miRnome. Aim 3. Define e-cigarettes toxicants with potent impact on platelet-dependent disease and function. While e-cigarettes are known to be source of a large number of toxicants, such as cotinine and acrolein, nothing is known regarding their specific impact on platelet activation/disease. Therefore, the effect of the e-cigarette toxicants, alone or in combination, on platelet function and associated disease will be investigated. Collectively, these experiments will make significant contributions to the understanding of the consequences of e-cigarettes on platelet activation and cardiovascular human health, and the mechanism and toxicants by/through which they exert these effects, in a dose-, time-, device-, e-liquid- specific manner, in the context of sex.

尽管吸烟一直在下降，但电子烟的使用量也在增加，即使在Covid19期间 大流行。此外，即使传统吸烟对血栓形成的发病机理的贡献 疾病有充分的记录，电子烟参与此类疾病过程仍然未知。 因此，目前的应用概述了针对基本，机械和临床的研究 电子烟的不良健康影响的相关翻译方面，这是一种日益流行的形式 烟草，在血小板生物学，血栓疾病和性别的背景下，在设备和电子液体特异 方式。还建议以类似的方式调查电子烟基础的毒物 效果。考虑到电子烟的“感知安全性”，这些研究至关重要。目的 该建议是： 目标1。研究电子烟暴露对血小板依赖性疾病状态的影响。那里 有令人信服的证据表明电子烟会产生负面影响，对血小板依赖的影响 疾病仍然未知。为了解决这些问题，电子烟暴露在正常情况下的后果 止血将以剂量和时间依赖的方式确定。随后的研究将检查 电子烟是否参与血栓形成疾病的发展。最后，设计实验 一种解决设备作用以及电子液体在电子烟效应中的作用的方式，性别为生物学 多变的。 目标2。研究电子烟调节血小板功能的机制。即使 初步数据表明，电子烟会调节止血，即调节的机制 血小板功能仍有待研究。这，本节提出的实验的总体目标是 为了确定电子烟暴露对各种血小板功能反应的影响，生化/等离子体 血栓形成的“标记”，对PGI2的机械耐药性以及是否介导了受体。 最后，提出了研究以确定电子烟是否在调节血小板miRNOME。 目标3。定义电子烟有毒物质，对血小板依赖性疾病和功能有潜在影响。尽管 众所周知，电子烟是大量毒物的来源，例如可替宁和丙烯醛，没有什么 知道它们对血小板激活/疾病的特定影响。因此，电子烟的效果 将研究毒物，单独或组合血小板功能和相关疾病。 总的来说，这些实验将为理解 电子烟对血小板激活和心血管人类健康的后果，以及 机理和有毒物质通过/通过，在剂量，时间，设备，e-liquid-中执行这些效果 特定的方式，在性别的背景下。