Although life expectancy for patients with Marfan syndrome has increased significantly over the past decades, aortic dissection continues to incur high morbidity/mortality. To date, prophylactic aortic root replacement remains the only proven treatment option to reduce the risk of type A aortic dissection.

In this project, we are making use of a range of mouse models carrying genetically engineered defects in the fibrillin-1 gene to study the cellular mechanisms leading to thoracic aortic wall damage which culminates in aortic dissection. In our preliminary studies, we have found that specific immune cell types are associated with different stages of aortic wall damage. We are proposing to further characterize the detailed properties of these immune cell populations, and to examine which role they play during the different stages of aortic disease. We plan to test whether targeting these cells will prevent or ameliorate the development of aortic wall damage in our mouse models. Finally, we will test whether we can identify signatures of these specific immune cell populations in thoracic aortic samples from patients with Marfan syndrome.

Taken together, our data provide the first known direct link between a defect in the fibrillin-1 gene and the recruitment and activation of specific immune cell types to the thoracic aorta. This project aims to leverage these findings to develop novel treatment options for the prevention of aortic dissection in Marfan syndrome.