Translational Research of Negative Emotions and Acute Endothelial Dysfunction

负面情绪与急性内皮功能障碍的转化研究

基本信息

批准号：
8790765
负责人：
DAICHI SHIMBO
金额：
$ 62.95万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-02-01 至 2016-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8790765
关键词：
Acute Address Adult Adverse effects Affect Anger Anxiety Arterial Fatty Streak Atherosclerosis Biological Blood Blood Vessels Bone Marrow Cardiovascular Diseases Cardiovascular system Critical Pathways Data Deposition Depressed mood Developed Countries Development Diffuse Disease Early identification Emotions Endothelial Cells Endothelin-1 Endothelium Evaluation Event Functional disorder General Population Health Human Incidence Individual Investigation Laboratories Link Lipids Mediating Mediator of activation protein Molecular Morbidity - disease rate N,N-dimethylarginine Nitric Oxide Oxidative Stress Participant Pathway interactions Patient Self-Report Play Prevention strategy Process Public Health Randomized Research Risk Risk Factors Role Stem cells Testing Thrombus Time Translational Research United States Vascular Endothelial Cell Vasodilation anxious base biological adaptation to stress cardiovascular disorder risk cell injury endothelial dysfunction experience hemodynamics hypothalamic-pituitary-adrenal axis inhibitor/antagonist injured mortality novel population based research study trait

项目摘要

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.

描述（由申请人提供）：负面情绪的经历与动脉粥样硬化相关的心血管疾病（CVD）事件的风险增加，与传统风险因素无关。支持这种关系的最强数据是引起愤怒。还有一些证据表明，急性抑郁或焦虑也是事件CVD的触发因素。基本的推定机制知之甚少。血管内皮细胞（EC）在维持血管张力和血管完整性中起着至关重要的作用。证据表明，内皮功能障碍是动脉粥样硬化发育和CVD事件发作的早期病原过程。这项研究的目的是主要检查引发愤怒的急性影响，其次是情绪和焦虑对EC健康的焦虑。对这些关键途径的检查将有助于确定内皮功能障碍是否是将核心负面情绪经验和事件CVD风险的经验联系起来的生物学机制。在此应用中，提出了一个最先进的，基于实验室的，随机对照实验的实验，该实验将测试引起的愤怒，情绪低落和焦虑是否会引起人类内皮功能障碍。我们假设这与情绪中立的状况相比。愤怒的召回任务将损害内皮依赖性的血管舒张，伤害EC并降低EC的恢复能力。我们还将研究情绪和焦虑感应任务抑郁是否会类似地诱发内皮功能障碍，以及引发自我报告的愤怒，情绪低落和焦虑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，我们将探讨否则不抑制是否部分介导了令人发指的愤怒，情绪抑郁，情绪抑制和对内皮功能的焦虑的急性不良影响。在美国，与动脉粥样硬化有关的CVD事件仍然是发病率和死亡率的主要原因。此外，愤怒，情绪低落和焦虑是成年人通常每天经历的负面情绪。因此，对这些假设的评估是及时且非常重要的，因为它将有助于确定推定的生物学途径将核心负面情绪的经验与CVD发病率联系起来，对于大量患有CVD事件风险增加的人。