University of Kentucky- Baylor College of Medicine Aortopathy Research Center

The University of Kentucky-Baylor College of Medicine Aortopathy Research Center (UK-BCM ARC) is a proposed new research network to define mechanisms of sex differences in thoracic aortic aneurysm and dissection. Thoracic aortic aneurysm and dissection have sexual dimorphism in humans. Pronounced differences between male and female have also been discerned in multiple mouse models of thoracic aortic aneurysms. The overall theme and mission of this center is to determine the contribution of hormonal and chromosomal sex differences to thoracic aortic aneurysm and dissection, with an emphasis on the role of extracellular matrix integrity. This Center builds on the complementary work of three principal investigators who have long track records of leading productive research programs in the field and who have built a strong collaborative network across institutions. Two basic science projects and one clinical project were proposed. Project 1 (Basic science; PI: Alan Daugherty) will determine whether sex hormonal status contributes to thoracic aortic aneurysms and dissection using two well-established thoracic aortopathy mouse models (angiotensin II infusion or fibrillin-1 hypomorphism) and two newly developed mouse models (fibrillin-1 floxed mice with fluorescent marker or elastin floxed mice). Project 2 (Basic science; PI: Lisa A. Cassis) will define whether X or Y chromosome and their related gene titration contribute to sex differences of thoracic aortic aneurysms using angiotensin II (AngII)-infused mouse model. Project 3 (Clinical study; PI: Scott LeMaire) will focus on determining whether mechanisms that relate to sex hormones and sex chromosomes in mouse models are associated with the thoracic aortopathy in humans. The proposed UK-BCM ARC brings together an institute with a strong history of basic research in aortopathy and an expanding clinical research program (UK), and an institute (BCM) that has strong translational and clinical research associated with one of the largest clinical programs in aortopathies in the country. The faculty of the proposed Center have had a long history of collaborations across institutes. The Center members are highly committed to interact with other members of the Network. We also emphasize the importance to train young investigators in this program. This ARC is poised to provide a leadership role in synergistically advancing progress in aortopathies through focused research and training across institutions.