Translational Research of Negative Emotions and Acute Endothelial Dysfunction

描述（由申请人提供）：负面情绪的经历与动脉粥样硬化相关心血管疾病（CVD）事件的风险增加相关，与传统风险因素无关。支持这种关系的最有力的数据是被激怒的愤怒。也有一些证据表明，变得严重抑郁或焦虑也是CVD事件的触发因素。潜在的假定机制知之甚少。血管内皮细胞（EC）在维持血管张力和血管完整性方面起着至关重要的作用。有证据表明，内皮功能障碍是动脉粥样硬化发展和CVD事件发生的早期致病过程。本研究的目的是初步探讨急性影响挑起愤怒，其次是抑郁情绪和焦虑对EC的健康。这些关键途径的检查将有助于确定内皮功能障碍是否是一种生物学机制，将核心负面情绪的经历与CVD风险联系起来。在本申请中，提出了一种最先进的、基于实验室的随机对照实验，该实验将测试激发的愤怒、抑郁情绪和焦虑是否会诱导人类内皮功能障碍。我们假设，与情绪中性条件相比，愤怒回忆任务会损害内皮依赖性血管舒张，损伤EC，并降低EC修复能力。我们还将研究抑郁情绪和焦虑诱导任务是否同样会诱导内皮功能障碍，以及激发的自我报告的愤怒，抑郁情绪和焦虑水平是否与内皮功能障碍的程度相关。最后，考虑到内源性一氧化氮（NO）抑制在加重内皮功能障碍中起着核心作用，我们将探讨NO抑制是否部分介导了激发愤怒、抑郁情绪和焦虑对内皮功能的急性不良影响。在美国，动脉粥样硬化相关的CVD事件仍然是发病率和死亡率的主要原因。此外，愤怒、抑郁情绪和焦虑是普通人群中成年人日常生活中常见的负面情绪。因此，对这些假说的评价是及时的和非常重要的，因为它将有助于确定一个假定的生物学途径 将核心负面情绪的经历与CVD发病率联系起来，对于大量CVD事件风险增加的个体来说。

DESCRIPTION (provided by applicant): The experience of negative emotions is associated with an increased risk of incident atherosclerosis-related cardiovascular disease (CVD) events, independent of traditional risk factors. The strongest data supporting this relation is with provoked anger. There is also some evidence that becoming acutely depressed or anxious are also triggers of incident CVD. The underlying putative mechanisms are poorly understood. Vascular endothelial cells (ECs) play an essential role in maintaining vascular tone and the integrity of blood vessels. Evidence suggests that dysfunction of the endothelium is an early pathogenic process underlying atherosclerosis development and CVD event onset. The aims of this study are to primarily examine the acute effects of provoked anger and secondarily depressed mood and anxiety on EC health. Examination of these critical pathways will help determine whether endothelial dysfunction is a biological mechanism linking the experience of core negative emotions and incident CVD risk. In this application, a state-of-the-art, laboratory-based, randomized controlled experiment is proposed that will test whether provoked anger, depressed mood and anxiety will induce endothelial dysfunction in humans. We hypothesize that compared to an emotionally neutral condition; an anger recall task will impair endothelium-dependent vasodilatation, injure ECs, and reduce EC reparative capacity. We will also examine whether a depressed mood and anxiety induction task will similarly induce endothelial dysfunction, as well as whether levels of provoked self-reported anger, depressed mood, and anxiety are associated with the degree of endothelial dysfunction. Finally, given that endogenous nitric oxide (NO) inhibition plays a central role in exacerbating endothelial dysfunction, we will explore whether NO inhibition partially mediates the acute adverse effects of provoked anger, depressed mood, and anxiety on endothelial function. In the United States, atherosclerosis-related CVD events remain the leading cause of morbidity and mortality. Further, anger, depressed mood, and anxiety are negative emotions commonly experienced by adults in the general population on a day-to-day basis. Therefore, evaluation of these hypotheses is timely and highly significant, as it will help identify a putative biological pathway linking the experience of core negative emotions to CVD incidence, for a large number of individuals who are at increased risk for CVD events.