The Effects of Shear Stress on Fibrillin-1 Production if Marfan Syndrome Endothelial Cells

Eli Brody

Mentor: Dr. Sharon Gerecht

Supervisor: Franklyn Hall

Institution: Institute for NanoBioTechnology, Johns Hopkins University

Marfan syndrome affects an estimated one in five thousand people in the U.S. making it one of the more common genetic mutations. While the majority of cases of Marfan syndrome are not fatal, it can lead to severe health issues such as thoracic aortic aneurysm which is the rapid swelling in the upper part of the heart’s main artery. Aortic aneurysm and many other health issues caused by Marfan syndrome result from blood vessel’s lack of structural proteins and, therefore, compromised elasticity. In order to better understand how Marfan syndrome affects blood vessel and cell structure, my research hopes to recreate the environment which mutated cells are exposed to. This includes the stresses imposed on the cells depending on their type and location. For my research, I am going to focus on endothelial cells (ECs) that line blood vessels. The main stresses experienced by ECs are shear stress caused by a liquid passing over the cells, and circumferential stress caused by the expanding of blood vessels as the heart pumps blood. My research will focus on the effects of shear stress on mutated versus healthy ECs. My research hopes to discover how Fibrilin-1 and other protein production is affected by shear stress in Marfan endothelial cells as compared to healthy endothelial cells. This research may give key insight into how different cell types in persons with Marfan syndrome react to their environments as well as offering a model of blood vessels in Marfan patients.