Defining the Impact of E-Cigarettes on Cardiac Pathophysiology

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CV不良结局相关，其特征为炎症增加。和随后 胶原沉积最近，引入了一种新的排放源，即电子烟（EC），并且 尤其是在年轻人中获得了前所未有的人气。虽然电子烟是一种人造的 尼古丁的来源类似于烟草香烟，它们是潜在有毒气体，细颗粒， 和尼古丁。然而，电子烟的使用是否会长期增加炎症和纤维化， 导致心脏和血管系统的结构和功能损伤;这些关键问题将得到回答 通过使用体内模型和首次使用原代人肌细胞的本提议。气溶胶从 EC由细颗粒和超细颗粒组成，这使得研究EC的合理效应相关 暴露对炎症和钙调节通路的影响。我们团队的研究表明， 细颗粒物会导致长期的心脏功能障碍。事实上，我们的数据是第一次检查 暴露于PM2.5的不良CV后果，并将扩展至包括关于EC的类似研究- 产生的气溶胶。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，但考虑到 越来越多的人口已经暴露于EC气溶胶，这是至关重要的，我们现在翻译我们的研究，以确定 对关键替代心肌细胞群的影响。我们已经建立了一个关键心脏细胞的活细胞库 非衰竭和患病的人类心脏。我们将充分利用这一点， 在小鼠和人类中进行平行功能实验的资源。我们假设EC气溶胶 促进对多种心脏细胞群的急性和慢性损伤，导致严重的器官和 有机体功能障碍本研究的目的是确定EC气雾剂的影响（在临床上- 相关浓度）对动物和良好表型的人心肌细胞的影响。我们将1）定义在 急性和慢性EC气溶胶暴露对心脏生理学的体内影响，2）确定急性和慢性EC气溶胶暴露对心脏生理学的影响， 慢性EC气溶胶暴露对关键心脏细胞群功能的影响，以及3），确定EC的影响 气溶胶暴露对关键的原代人类心脏细胞群的影响。

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.