Defining Novel Roles of Platelets and Macrophages in the Healing of Abdominal Aortic Aneurysm

ABSTRACT (Project Summary) Rupture of abdominal aortic aneurysms (AAA) leads to sudden death in 15,000 to 30,000 men and women over the age of 65 each year in the US, and this number is growing due to both an increase in the elderly population and our increasingly poor life-style choices, e.g. sedentary lifestyle and western diet, resulting in

cardiovascular disease. Known risk factors for AAA include advanced age, tobacco use, male gender, and cardiovascular disease. However, the underlying cause of this condition is still poorly understood. Recent evidence demonstrated accelerated AAA growth is associated with platelet activation and platelet aggregates

(thrombi) in aneurysmal segments. Studies have shown that platelets are critically important to the formation and progression of abdominal aortic aneurysm (AAA). We speculate this occurs via a platelet-derived network of monocyte and macrophage activation. To date, little progress has been made to identify any pharmacologic

treatments which may benefit AAA patients leaving surgery as the only treatment option. The broad, long-term goal of this proposal is to define the mechanisms by which platelets may regulated monocyte/macrophage interactions at the site of AAA injury and to develop new and innovative tools to harness this knowledge via

reparative tissue regeneration and de novo morphogenesis. Our team will test they hypothesis that platelet – leukocyte interactions and cross-talk in a regenerative animal model will provide a blueprint for site-specific regeneration and healing of cardiovascular damaged tissues, specifically AAA. Our overall project combines

unique animal models and transgenic lines and new interdisciplinary collaborations to accomplish our goals. Ultimately, our discoveries obtained utilizing this highly flexible Exploratory/Developmental Award will support the stated mission of the NIA to extend the healthy, active years of life, and may lead to revolutionary medical

approaches for dealing with an, as yet, intractable disease state.