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.

在此应用中，我建议致力于感知和了解缺血性心脏病中的先天免疫力。 我将问一个总体问题心血管疾病，更具体地说是风险因素 高血压会影响造血，即骨髓中的先天免疫细胞产生。我建议 解决两个主要目标：1。开发和验证基本科学和翻译成像工具 提供有关骨髓造血的体内数据，包括浸润显微镜和正电子发射 断层扫描/磁共振成像； 2。破译缺血性心脏病如何改变骨头 骨髓功能和器官的炎性免疫细胞输出。我的直接重点是骨头 骨髓脉管系统。这种重点是由血管干细胞生态裂的影响所激发的，这指示 造血干细胞增殖，祖细胞谱系偏置和白细胞迁移。同时， 骨髓脉管系统是全身循环的一部分，因此暴露于心血管风险和 促进疾病的途径。尚不清楚骨髓脉管是否以及缺血性心脏的变化 疾病以及这些变化如何调节全身先天免疫细胞供应。受到证据的动机 系统性白细胞水平与心血管死亡率相关，我将解决这一知识差距 发现动脉粥样硬化患者的新治疗靶标的最终目标。