Stress-induced immune reprogramming in cardiovascular disease

项目摘要 心理社会压力是心血管疾病的关键危险因素。但目前的 心血管风险管理策略包括很少的循证干预措施， 心理压力对这种疾病的有害影响随着当前的全球事件，特别是 持续的COVID-19大流行和不断增加的动脉粥样硬化性心脏病负担， 压力的影响是有道理的。我们当前提案的目标是机械地理解心理社会学 应激对免疫系统的影响和炎症性动脉粥样硬化降低残余心血管 患者的风险。 在我们的第一类计划的过程中，我们对有关联系的知识做出了很大贡献。 社会心理压力和心血管疾病之间的联系， 连接神经免疫和血管系统的通路。具体来说，我们发现压力 感知机制影响动脉粥样硬化的发展和消退。我们开发 复杂的工具来研究特定的大脑区域及其对压力感知的贡献。我们做 动脉粥样硬化的平移成像研究取得实质性进展。在临床研究中， 基于对神经免疫动脉通路的理解。 我们共同努力研究压力如何影响免疫系统， 我们现在渴望探索的创新研究问题。根据我们的第1类计划，在当前 我们将不仅仅研究巨噬细胞生物学;我们将扩大我们的范围， 心理社会压力加剧的动脉粥样硬化疾病中免疫重编程的完整图片。我们 该计划更广泛的视角包括更广泛地评估不同的大脑回路， 多种成像方法，同时追求更深入的分析（组学）和最佳数据 一体化这种创新的方法将提高我们对复杂的相互关系， 压力感知和心血管免疫学，同时扩大了该计划的临床范围。 我们将与我们的多学科团队，包括 前一个项目的主要研究人员，其主要研究人员，以及新的合作者， 神经科学，精神病学，和训练的免疫力。我们的节目将提供关键的见解如何压力- 诱导的免疫重编程加剧（正在进行的）心血管疾病。圆满完成 将不仅为独特的（i）对免疫机制的科学见解奠定基础， 神经和驱动心血管疾病的发展，但也产生（ii）前瞻性思维的方法 在经历长期心理社会压力的个体中管理心血管疾病 并确定新的（iii）治疗靶点和治疗方法。

PROJECT SUMMARY Psychosocial stress is a critical risk factor for cardiovascular disease. However, current cardiovascular risk management strategies include few evidence-based interventions to address psychosocial stress’s detrimental effects on this disease. With the current global events, notably the ongoing COVID-19 pandemic and the increasing burden of atherosclerotic heart disease, modulating stress’ effects is warranted. The goal of our current proposal is mechanistically understanding psychosocial stress’s impact on the immune system and inflammatory atherosclerosis to lower residual cardiovascular risk in patients. Over the course of our Type-1 Program, we substantially contributed to knowledge about the links between psychosocial stress and cardiovascular disease by identifying tissular, cellular, and molecular pathways that connect nervous, immune, and vascular systems. Specifically, we found that stress perception mechanisms influence atherosclerosis development and regression. We developed sophisticated tools to study specific brain regions and their contributions to stress perception. We made substantial progress on translational imaging studies in atherosclerosis. In clinical studies, we are gaining ground on understanding the neuro-immune-arterial pathway. Our collaborative efforts to studying how stress affects the immune system have yielded new, innovative research questions we are now eager to explore. Drawing on our Type-1 Program, in the current proposal, we will not merely investigate macrophage biology; we will broaden our scope to acquire a complete picture of immune reprogramming in psychosocial stress-aggravated atherosclerotic disease. Our Program’s broader perspective includes more expansively evaluating different brain circuits and employing a wide variety of imaging methods while pursuing more in-depth analyses (omics) and optimal data integration. This innovative approach will elevate our understanding of the complex interrelation between stress perception and cardiovascular immunology, simultaneously extending the Program’s clinical scope. We will approach this highly innovative program with our multidisciplinary team including the previous program’s principal investigators, most of its key investigators, as well as new collaborators in neuroscience, psychiatry, and trained immunity. Our program will yield critical insights into how stress- induced immune reprogramming exacerbates (ongoing) cardiovascular disease. Its successful completion will not only lay the foundation for unique (i) scientific insights into immune mechanisms that are regulated neurologically and drive cardiovascular disease development but also yield (ii) a forward-thinking approach to managing cardiovascular disease in individuals experiencing prolonged episodes of psychosocial stress and identify novel (iii) therapeutic targets and treatments.