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/?cnull/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.
Cardiovascular diseases (CVD) account for one-third of annual deaths globally, with the incidence of CVD increasing with advanced age. Chronic inflammation of the arteries contributes to the vascular dysfunction dominant in CVD, but the link between the two has yet to be elucidated. The proposed study will provide information as to whether T cells from aged individuals, and therefore their immune systems, can directly mediate vascular dysfunction in the absence of an aged and altered arterial wall, providing a potential target for age-related arterial dysfunction and CVD.
