Stress perception and cardiovascular immunology

项目1摘要 心理社会压力对心血管健康有重大影响。在过去5年的PPG中，我们 确定了组织，细胞和分子通路，连接神经，免疫和血管系统， 应力在这次更新中，我们将重点关注识别将大脑区域与 在心血管疾病的发展过程中，血管壁会发生变化。我们将扩大研究范围， 神经免疫和神经血管连接在不同的压力感知背景下发生改变。 具体地说，我们将首先寻求确定大脑回路和外围通路连接心理社会压力， 心血管疾病，然后阐明弹性与社会失败压力的易感性如何形成 心血管疾病中脑与外周的通讯及其解决方案。我们将建立在 初步数据显示，急性应激诱发了四种主要白细胞的深刻空间重组， 类，其特征在于淋巴和髓样细胞的大量迁移，已知在 心血管疾病，并注意到动脉粥样硬化进展之间存在重要差异 有弹性和易受影响的小鼠。我们假设不同的大脑区域动态调节单核细胞， 中性粒细胞和淋巴细胞的功能和空间分布，影响发展，进展， 动脉粥样硬化的并发症，这些途径中的一个或多个在社会失败压力期间是至关重要的。 我们将使用复杂的方法和模型，包括光遗传学和化学遗传学。一起我们 将阐明沟通网络连接大脑与血管和动脉粥样硬化过程中， 适应力和对社会压力的敏感性。

SUMMARY FOR PROJECT 1 Psychosocial stress has a major impact on cardiovascular health. Over the last 5 years of this PPG, we have identified tissue, cellular, and molecular pathways that connect nervous, immune, and vascular systems during stress. In this renewal, we will focus on identifying specific nodes of communication that link brain regions with the vessel wall during the progression of cardiovascular disease. We will broaden our studies to explore how neuroimmune and neurovascular connections are altered in the context of different stress perceptions. Specifically, we will first seek to identify brain circuits and peripheral pathways linking psychosocial stress with cardiovascular disease and then elucidate how resilience vs susceptibility to social defeat stress shapes communication between brain and periphery in cardiovascular disease and its resolution. We will build on preliminary data showing that acute stress elicits a profound spatial reorganization of four major leukocyte classes, characterized by a mass migration of lymphoid and myeloid cells known to be important in cardiovascular disease and noting that there is important difference in atherosclerosis progression between resilient and susceptible mice. We hypothesize that distinct brain regions dynamically regulate monocyte, neutrophil, and lymphocyte function and spatial distribution, influencing the development, progression, and complications of atherosclerosis and that one or more of these pathways is critical during social defeat stress. We will use sophisticated approaches and models, including optogenetics and chemogenetics. Together, we will elucidate the communication network linking the brain with the vasculature and atherosclerosis during resilience and susceptibility to social stress.