Defining the Impact of E-Cigarettes on Cardiac Pathophysiology

定义电子烟对心脏病理生理学的影响

• 批准号: 9413642
• 负责人: Loren Eugene Wold
• 金额: $ 38.79万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-15 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9413642
• 关键词: Acute; Adult; Aerosols; Air Pollution; Animal Disease Models; Animals; Apoptosis; Area; Biochemistry; Calcium; Cardiac; Cardiac Myocytes; Cells; Cellular biology; Chronic; Cigarette; Collagen; Complex; Data; Defect; Deposition; Electronic cigarette; Exposure to; Fibrosis; Functional disorder; Gases; Genetic Transcription; Goals; Heart; Human; Image; Inflammation; Inflammatory; Investigation; Link; Mediator of activation protein; Minor; Molecular; Mus; Muscle Cells; Myocardial; Myocardial dysfunction; Necrosis; Nicotine; Organ; Organism; Outcome; Particulate; Particulate Matter; Pathway interactions; Phenotype; Physiology; Population; Productivity; Regulatory Pathway; Research; Research Infrastructure; Resources; Rodent; Scientist; Signal Transduction; Source; System; Techniques; Testing; Time; Tobacco; Translating; Ultrafine; base; clinically relevant; design; experimental study; exposed human population; fine particles; high risk; human disease; in vivo; in vivo Model; particle; programs; repository; ultrafine particle

Project Summary/Abstract Both cigarettes and air pollution are sources of toxic gases and fine particulate matter (PM2.5; particles <2.5 µm) that are linked with adverse CV outcomes, characterized by increased inflammation. and subsequent collagen deposition. Recently, a new source of emissions, the electronic cigarette (EC), was introduced and is gaining unprecedented popularity, especially among young people. Although e-cigarettes are an artificial source of nicotine similar to tobacco cigarettes, they are a source of potentially toxic gases, fine particulates, and nicotine. However, it remains unknown if e-cigarette use increases inflammation and fibrosis long-term, leading to structural and functional damage to heart and vasculature; these critical questions will be answered by the present proposal using in vivo models and, for the first time, primary human myocytes. Aerosol from ECs are comprised of fine and ultrafine particles which makes it relevant to investigate plausible effects of EC exposure on inflammatory and calcium regulatory pathway. Studies from our team demonstrate that exposure to fine particulate matter cause long-term cardiac dysfunction. In fact, our data are the first to examine the adverse CV consequences of exposure to PM2.5, and will be expanded to include similar studies on EC- generated aerosol. While our findings in mice support the critical impact of EC aerosol in mice, given the growing population already exposed to EC aerosols, it is critical that we now translate our studies to define the impact on key surrogate cardiac cell populations. We have established a live cell repository of key cardiac cell populations from non-failing and diseased human heart. We will take advantage of this now well validated resource to perform parallel functional experiments in both mice and human. We hypothesize that EC aerosol promotes both acute and chronic damage to multiple cardiac cell populations resulting in severe organ and organism dysfunction. The goals of this investigation are to define the impact of EC aerosol (in clinically- relevant concentrations) on animals and well phenotyped human cardiac myocytes. We will 1) define the in vivo impact of acute and chronic EC aerosol exposure on cardiac physiology, 2) define the impact of acute and chronic EC aerosol exposure on the function of key cardiac cell populations, and 3), Define the impact of EC aerosol exposure on key primary human cardiac cell populations.

项目摘要/摘要 香烟和空气污染都是有毒气体和细颗粒物的来源（PM2.5；颗粒 <2.5 µm）与不良CV结果有关，其特征是注射量增加。然后 胶原蛋白沉积。最近，引入了一种新的排放来源，电子民用（EC），并且是 获得前所未有的流行，尤其是在年轻人中。虽然电子烟是人造的 尼古丁的来源类似于烟草香烟，它们是潜在有毒气体的来源，细成分， 和尼古丁。但是，尚不清楚电子烟的使用是否会增加影响和纤维化长期， 导致对心脏和脉管系统的结构和功能损害；这些关键问题将得到回答 通过本建议，使用体内模型，这是初级人类肌细胞。气雾剂来自 EC由细和超细颗粒组成，这使得研究EC的合理效应与 暴露于炎症和钙调节途径。我们团队的研究证明了这种曝光 细颗粒物会引起长期心脏功能障碍。实际上，我们的数据是第一个检查 暴露于PM2.5的不利CV后果，并将扩展到包括有关EC-的类似研究 生成的气溶胶。虽然我们在小鼠中的发现支持EC气溶胶对小鼠的关键影响，但鉴于 不断增长的人口已经暴露于EC气溶胶，至关重要的是，我们现在将研究转化为定义 对关键替代心脏细胞群体的影响。我们已经建立了关键心脏细胞的活细胞存储库 来自非手机和失调的人类心脏的种群。我们将利用这一点，现在得到了良好的验证 在小鼠和人类中执行并行功能实验的资源。我们假设EC气溶胶 促进对多个心脏细胞群体的急性和慢性损害，导致严重器官和 生物功能障碍。这项研究的目标是定义EC气溶胶的影响（在临床上 - 相关浓度）对动物和表现良好的人心肌细胞。我们将1）定义 急性和慢性EC气溶胶暴露对心脏生理学的体内影响，2）定义急性和 慢性EC气溶胶暴露于关键心脏细胞群体的功能，3）定义了EC的影响 在关键的原发性人类心脏细胞种群上暴露气溶胶。