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

项目摘要/摘要

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.