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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.

项目总结/文摘