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

基本信息

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
项目类别：
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

项目摘要

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.

项目概要/摘要香烟和空气污染都是有毒气体和细颗粒物（PM2.5；颗粒物）的来源 <2.5 µm），与不良心血管结果相关，其特征是炎症增加和随后的炎症。最近，出现了一种新的排放源——电子烟（EC）。尽管电子烟是一种人造烟，但它获得了前所未有的普及，尤其是在年轻人中。尼古丁的来源与烟草香烟类似，它们是潜在有毒气体、细颗粒物的来源，然而，电子烟的使用是否会长期增加炎症和纤维化仍然未知。导致心脏和脉管系统的结构和功能损伤；这些关键问题将得到解答；根据目前的建议，首次使用来自气溶胶的体内模型和原代人类肌细胞。 EC 由细颗粒和超细颗粒组成，这使得研究 EC 的合理影响具有相关性我们团队的研究表明，暴露对炎症和钙调节途径的影响。事实上，我们的数据是第一个检验细颗粒物导致长期心脏功能障碍的。暴露于 PM2.5 的不良 CV 后果，并将扩大到包括 EC- 虽然我们在小鼠身上的研究结果支持 EC 气溶胶对小鼠的关键影响，但考虑到随着越来越多的人口已经暴露于 EC 气溶胶，我们现在将我们的研究成果转化为定义对关键替代心肌细胞群的影响我们建立了关键心肌细胞的活细胞库。我们将利用现已得到充分验证的这一点。在小鼠和人体中进行平行功能实验的资源我们追求 EC 气雾剂。促进多个心肌细胞群的急性和慢性损伤，导致严重的器官和疾病这项研究的目标是确定 EC 气溶胶的影响（在临床上）。相关浓度）在动物和表型良好的人类心肌细胞上我们将1）定义in。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 气溶胶暴露的影响慢性 EC 气溶胶暴露对关键心肌细胞群功能的影响，以及 3)、定义 EC 的影响关键原代人类心肌细胞群的气溶胶暴露。