Defining the Impact of E-Cigarettes on Cardiac Pathophysiology

项目摘要/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 &lt；2.5微米)，与不良的CV结果相关，其特征是炎症增加。以及随后的 胶原蛋白沉积。最近，一种新的排放源--电子烟(EC)被引入并被 获得前所未有的人气，特别是在年轻人中。尽管电子烟是一种人造烟 尼古丁的来源类似于烟草香烟，它们是潜在有毒气体、细颗粒物、 还有尼古丁。然而，目前还不清楚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害；这些关键问题将得到解答 通过目前的建议，使用活体模型，并首次使用原代人类心肌细胞。气雾剂来自 EC由细小和超细颗粒组成，这使得研究EC的可能影响具有重要意义 暴露在炎症和钙调节途径上。我们团队的研究表明，暴露在 细颗粒物会导致长期的心脏功能不全。事实上，我们的数据是第一个检查 暴露于PM2.5的不良心血管后果，并将扩大到包括类似的研究EC- 产生的气溶胶。虽然我们在小鼠身上的发现支持EC气雾剂对小鼠的关键影响，但鉴于 越来越多的人已经暴露在EC气溶胶中，我们现在将我们的研究转化为定义 对关键的代用心脏细胞种群的影响。我们已经建立了一个关键心脏细胞的活细胞库 来自不衰竭和有病的人类心脏的人群。我们将利用这一点，现在已经得到了很好的验证 在小鼠和人类身上进行平行功能实验的资源。我们假设EC气雾剂 促进对多种心脏细胞群的急性和慢性损害，导致严重的器官和 机体功能障碍。这项研究的目标是确定EC气雾剂的影响(在临床上- 相关浓度)对动物和表型良好的人心肌细胞。我们将1)定义In 急性和慢性EC气雾剂暴露对心脏生理的活体影响，2)确定急性和慢性EC气雾剂暴露对心脏生理的影响 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 气溶胶暴露对主要原代人类心脏细胞种群的影响。

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.