IMPACT OF T CELLS ON AGE-RELATED VASCULAR DYSFUNCTION: A TRANSLATIONAL APPROACH - DIVERSITY SUPPLEMENT

T 细胞对年龄相关血管功能障碍的影响：转化方法 - 多样性补充

• 批准号: 10168869
• 负责人: Anthony John Donato
• 金额: $ 4.46万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-15 至 2023-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10168869
• 关键词: Acute; Age; Anti-Inflammatory Agents; Aorta; Arteries; Automobile Driving; Biological Availability; Blood Vessels; Cardiovascular Diseases; Cell Aging; Cells; Cessation of life; Chronic; Data; Elderly; Endothelium; Functional disorder; Future; Genetic Models; Home environment; Human; Hypertension; Immune; Immune response; Immune system; Immunodeficient Mouse; Incidence; Individual; Infiltration; Inflammation; Inflammatory; Link; Mediating; Mus; Nitric Oxide; Play; Process; Resistance; Rodent Model; Role; Sterility; T cell therapy; T-Lymphocyte; Testing; Tissues; Tumor-infiltrating immune cells; Vascular Diseases; Vasodilation; age related; aged; arterial stiffness; cardiovascular disorder risk; cardiovascular risk factor; cell age; cytokine; experience; healthy aging; humanized mouse; improved; innovation; mouse model; novel; recruit; translational approach; translational study

Project Summary/ Abstract Advanced age is a leading risk factor for cardiovascular diseases (CVD). As individuals age, they experience numerous vascular alterations which include increased arterial stiffness and reduced endothelial-dependent vasodilation. An underlying disturbance common in many CVDs is chronic inflammation; but its specific role has not been clearly elucidated. T cells play a central role in the immune response, and may be implicated in age-related arterial inflammation and the accompanying vascular dysfunction. We will employ a translational approach to examine the role of T cells in this process. We hypothesize that T cells from older human donors will home to the vasculature of humanized immuno-deficient mice and induce inflammation and subsequent arterial dysfunction. To test this, we will adoptively transfer T cells from young and older healthy human donors to young and old NOD-scid/γcnull/A2 humanized mice and assess immune cell infiltration, inflammation, arterial function, and ROS. This will allow us to assess the role of T cells per se, and discover their mechanistic function in the arterial dysfunction seen with age.

项目摘要/摘要 高龄是心血管疾病（CVD）的主要危险因素。随着个人的年龄，他们经历了 许多血管变化，包括增加动脉刚度和降低的内皮依赖性 血管舒张。在许多CVD中常见的一场基本灾难是慢性炎症。但是它的特定角色 尚未清楚地阐明。 T细胞在免疫反应中起着核心作用，可能与 与年龄相关的动脉注射和参与的血管功能障碍。我们将采用翻译 检查T细胞在此过程中的作用的方法。我们假设来自老年人供体的T细胞 将回到人性化免疫缺陷小鼠的脉管系统中，并诱导注射，然后 动脉功能障碍。为了测试这一点，我们将适当地转移来自年轻和年长健康的人类捐助者的T细胞 到年轻人和老年人scID/γcnull/a2人源化小鼠和评估免疫细胞浸润，炎症， 动脉功能和ROS。这将使我们能够评估T细胞本身的作用，并发现其机械 随着年龄的增长，动脉功能障碍的功能。