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)事件的风险增加有关，与传统的风险因素无关。支持这种关系的最有力的数据是激起的愤怒。也有一些证据表明，变得极度抑郁或焦虑也是引发心血管事件的原因。人们对潜在的推定机制知之甚少。血管内皮细胞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形成和心血管事件发生的早期致病过程。这项研究的目的是主要考察激怒和继发性抑郁情绪和焦虑对EC健康的急性影响。对这些关键途径的研究将有助于确定内皮功能障碍是否是一种将核心负面情绪的体验与心血管事件风险联系起来的生物机制。在这一应用中，提出了一种最先进的、基于实验室的随机对照实验，该实验将测试激怒、抑郁情绪和焦虑是否会导致人类的内皮功能障碍。我们假设，与情绪中立的情况相比，愤怒回忆任务将损害内皮依赖的血管扩张，损害内皮细胞，并降低内皮细胞的修复能力。我们还将研究抑郁情绪和焦虑诱导任务是否同样会导致内皮功能障碍，以及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相关。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普遍经历的负面情绪。因此，对这些假说的评估是及时和非常重要的，因为它将有助于确定一条假定的生物学途径。 将核心负面情绪的体验与心血管疾病的发病率联系起来，对于大量面临心血管事件风险增加的个人来说。

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.