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

项目总结/摘要 高龄是心血管疾病（CVD）的主要危险因素。随着年龄的增长， 许多血管改变，包括动脉僵硬度增加和内皮依赖性降低， 血管舒张许多CVD中常见的潜在障碍是慢性炎症;但其特定作用 还没有被清楚地阐明。T细胞在免疫应答中起着核心作用，并且可能与免疫应答有关。 与年龄相关的动脉炎症和伴随的血管功能障碍。我们将聘请翻译 研究T细胞在这一过程中的作用。我们假设来自老年人捐赠者的T细胞 将归巢于人源化免疫缺陷小鼠的脉管系统，并诱导炎症和随后的 动脉功能障碍为了测试这一点，我们将从年轻和老年健康的人类捐赠者中过继转移T细胞。 年轻和年老的NOD-scid/γcnull/A2人源化小鼠，并评估免疫细胞浸润，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，并发现其机制。 随着年龄的增长，动脉功能障碍。

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.