Marie Billaud, PhD
Hanjaaram Cha, Ryan Martinez, Kristen Liu, Susanna Lee, Colin Flaherty, Mariam Kerolos, Julie Phillippi, Marie Billaud
Research Category: Cardiovascular, Diabetes, and Metabolic Disorders
Ascending thoracic aortic aneurysms (ATAA) affect nearly 50,000 patients in the US yearly. Current research focuses on understanding the cellular pathophysiology of ATAA to uncover new therapeutic targets. Our objective is to collect new information related to smooth muscle cells (SMCs) metabolism in ATAA with a focus on two growth factors essential for their function. SMCs were obtained from human ATAA and non-aneurysmal specimens resected during cardiac surgery. Aneurysmal SMCs were more glycolytic than non-aneurysmal SMCs, but mitochondrial respiration was similar. PDGF-BB upregulated the expression of mitochondrial transcription factor only in aneurysmal SMCs from patients with bicuspid aortic valve (BAV), a common congenital anomaly and known risk factor for ATAA. This indicates that PDGF-BB may uniquely stimulate mitobiogenesis in BAV-associated ATAA. PDGF-BB and TGF-β1 reduced mitofusin 2 expression in non-aneurysmal and aneurysmal SMCs, but only in those from patient not affected with BAV, indicating that the growth factors may contribute to mitochondrial dynamics only in non BAV-associated ATAA. Experiments are ongoing to determine how TGF-β1 and PDGF-BB affect SMC contraction and mitochondrial function and structure. Future projects will identify the molecular players responsible for the distinct roles of TGF-β1 and PDGF-BB on SMCs in ATAA to identify new therapeutic targets.
Aortic aneurysm is an abnormal bulge of the aorta, the largest artery in the body, and affect approximately 50,000 people in the US each year. The only treatment available is open heart surgery to remove the aneurysmal aorta when the bulge reaches approximately twice the size of a normal aorta and replace it with a graft. However, open heart surgery can also lead to complications such as stroke. Our goal is to better understand the disease at a cellular level and uncover new therapeutic targets to slow or stop the progression of the disease and avoid surgery. In this project, we focused on how the cells making up the aorta produce energy. We used cells from aortas removed from consented patients undergoing cardiac surgery and found that cells from aneurysmal aorta prefer to use sugar to produce energy while non-aneurysmal cells prefer to use oxygen through the mitochondria. We also found that one growth factor produced by these cells increases the growth and multiplication of mitochondria in aneurysmal cells to form a large and efficient network for energy production. We hope to use these findings in the future to develop new treatments for patients affected with aortic aneurysms.