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）事件发生的风险增加有关，独立于传统的危险因素。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心血管疾病的诱因。人们对潜在的假定机制知之甚少。血管内皮细胞（ECs）在维持血管张力和血管完整性方面发挥着重要作用。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。本研究的主要目的是研究激怒性愤怒和继发性抑郁情绪和焦虑对EC健康的急性影响。检查这些关键通路将有助于确定内皮功能障碍是否是连接核心负面情绪体验和心血管疾病风险的生物学机制。在这个应用中，一个最先进的，基于实验室的，随机对照实验提出，将测试是否激怒愤怒，抑郁情绪和焦虑会诱导内皮功能障碍的人。我们假设，与情绪中立的情况相比；愤怒回忆任务会损害内皮依赖性血管舒张，损伤EC，降低EC的修复能力。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，以及被激怒的自我报告的愤怒、抑郁情绪和焦虑的水平是否与内皮功能障碍的程度有关。最后，鉴于内源性一氧化氮（NO）抑制在加剧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心血管疾病事件仍然是发病率和死亡率的主要原因。此外，愤怒、抑郁情绪和焦虑是成年人在日常生活中普遍经历的负面情绪。因此，对这些假设的评估是及时和高度重要的，因为它将有助于确定假定的生物学途径

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.