Imaging organ system interfaces in ischemic heart disease

缺血性心脏病中器官系统接口的成像

• 批准号: 10088460
• 负责人: Matthias Nahrendorf
• 金额: $ 98.57万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-02-01 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10088460
• 关键词: Address; Affect; Atherosclerosis; Blood Circulation; Blood Vessels; Bone Marrow; Cardiovascular Diseases; Cardiovascular system; Cells; Data; Disease; Exposure to; Goals; Hematopoiesis; Hematopoietic stem cells; Hypertension; Image; Imaging Device; Immune; Inflammatory; Knowledge; Leukocytes; Magnetic Resonance Imaging; Myocardial Ischemia; Natural Immunity; Organ; Output; Pathway interactions; Patients; Positron-Emission Tomography; Production; Risk Factors; Science; Time; Work; body system; cardiovascular risk factor; in vivo; intravital microscopy; migration; mortality; new therapeutic target; progenitor; stem cell niche; stem cell proliferation

In this application, I propose to work on sensing and understanding innate immunity in ischemic heart disease. I will ask the overarching question how cardiovascular disease, and more specifically the risk factor hypertension, affects hematopoiesis, i.e. innate immune cell production, in the bone marrow. I propose to tackle two major goals: 1. to develop and validate fundamental science and translational imaging tools that provide in vivo data on bone marrow hematopoiesis, including intravital microscopy and positron emission tomography/magnetic resonance imaging; 2. to decipher how ischemic heart disease disease alters bone marrow function, and the organ's output of inflammatory immune cells. My immediate focus will be the bone marrow vasculature. This focus is motivated by the influence of the vascular stem cell niche, which instructs hematopoietic stem cell proliferation, progenitor lineage bias and leukocyte migration. At the same time, the bone marrow vasculature is part of the systemic circulation, and therefore exposed to cardiovascular risk and disease-promoting pathways. It is unknown if and how bone marrow vasculature changes in ischemic heart disease, and how these changes modulate systemic innate immune cell supply. Motivated by evidence that systemic leukocyte levels correlate with cardiovascular mortality, I will address this knowledge gap with the ultimate goal to discover new therapeutic targets for patients with atherosclerosis.

在这个应用程序中，我建议工作的感知和理解先天免疫缺血性心脏病。 我会问一个至关重要的问题，心血管疾病，更具体地说， 高血压影响骨髓中的造血作用，即先天免疫细胞的产生。我建议 解决两个主要目标：1.开发和验证基础科学和转化成像工具， 提供骨髓造血的体内数据，包括活体显微镜检查和正电子发射 断层扫描/磁共振成像; 2.来解释缺血性心脏病如何改变骨骼 骨髓功能和器官的炎症免疫细胞输出。我现在的重点是骨头 骨髓脉管系统这一重点是由血管干细胞龛的影响，这指示 造血干细胞增殖、祖细胞谱系偏好和白细胞迁移。同时对 骨髓脉管系统是体循环的一部分，因此暴露于心血管风险， 疾病传播途径。缺血性心脏骨髓血管系统是否以及如何改变尚不清楚 疾病，以及这些变化如何调节系统性先天免疫细胞供应。有证据表明， 全身白细胞水平与心血管死亡率相关，我将通过 最终目的是为动脉粥样硬化患者发现新的治疗靶点。