Stress-induced immune reprogramming in cardiovascular disease

项目总结 心理社会压力是心血管疾病的关键风险因素。但是，当前 心血管风险管理策略中几乎没有循证干预措施。 心理社会压力对这种疾病的不利影响。当前的全球事件，值得注意的是 持续的新冠肺炎大流行和日益加重的动脉粥样硬化性心脏病负担，调节 压力的影响是理所当然的。我们目前的建议的目标是机械地理解心理社会 应激对免疫系统和炎性动脉粥样硬化的影响以降低残余心血管 患者的风险。 在我们的Type-1计划的过程中，我们对有关链接的知识做出了很大贡献 通过鉴定组织、细胞和分子在心理社会应激和心血管疾病之间的关系 连接神经、免疫和血管系统的通路。具体来说，我们发现压力 知觉机制影响动脉粥样硬化的发展和消退。我们开发了 先进的工具来研究特定的大脑区域及其对压力感知的贡献。我们做了 动脉粥样硬化的翻译成像研究取得实质性进展。在临床研究中，我们正在获得 以了解神经-免疫-动脉通路为基础。 我们合作研究压力如何影响免疫系统的努力取得了新的成果， 我们现在渴望探索的创新研究问题。利用我们的Type-1计划，在当前 提议，我们将不仅研究巨噬细胞生物学；我们将扩大我们的范围，以获得 心理社会应激加重动脉粥样硬化疾病的免疫重编程的完整图片。我们的 该计划更广阔的视角包括更广泛地评估不同的大脑回路，并利用 各种成像方法，同时追求更深入的分析(组学)和最佳数据 整合。这种创新的方法将提高我们对 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一起实施这一高度创新的计划，包括 之前项目的主要调查人员，大多数关键调查人员，以及 神经科学、精神病学和训练有素的免疫力。我们的节目将提供关于压力如何-的关键见解 诱导免疫重编程加剧(持续的)心血管疾病。它成功地完成了 不仅为对受调控的免疫机制的独特(I)科学见解奠定基础 神经学和推动心血管疾病的发展，但也产生(Ii)前瞻性思维方法 在经历长期心理社会应激的个人中管理心血管疾病 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.