Thesis: Studying the antithrombotic and hemostatic potential of valvular endothelial cells.
Most bioprosthetic valve implants eventually break down, and mechanical valve implants require medication due to the risk of blood clotting. This problem has generated interest in understanding how cells on the surface of valves, called valvular endothelial cells (VECs), naturally prevent clotting. My research will evaluate proteins secreted from VECs involved in this protective process. The balance between a particular clotting protein, von Willebrand Factor (VWF), and the enzyme that dissolves VWF, ADAMTS-13, is an important factor in clot formation. I will analyze how these proteins interact with the immediate environment of the VECs, including the forces due to blood flow and sticking to other proteins that anchor the cells to the rest of the valve. I aim to study the cells and tissues of normal and diseased heart valves using several methods to analyze the nanoscale interactions of VWF, ADAMTS-13, VECs, and surrounding anchor protein, as well as study how blood flow and anchoring proteins influence the capacity of VECs to retard clotting.