Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships

Thrombosis (the formation of pathological blood clots) is a leading cause of death worldwide. Obesity has become a global epidemic and is a major risk factor for thrombotic events including heart attacks, strokes and venous thrombosis. One reason for this is that obesity is associated with inflammation. von Willebrand factor (VWF) is a protein in the blood that assists blood clot formation through binding platelets (the primary cellular component of clots) to each other and to the blood vessel wall. VWF also binds to white blood cells to increase inflammation. Its function is regulated by another protein called ADAMTS13. It has been shown that high VWF levels in the blood are associated with an increased risk for thrombosis and VWF levels are elevated in patients with obesity. Our study will investigate the interrelationship between obesity and VWF in inflammation and thrombosis. The purpose of our research is: (1) to use cells and obese patient blood to look at the role of VWF to bind platelets and white blood cells; (2) to investigate how VWF influences inflammation in obese mice; (3) to evaluate whether changes in VWF directly cause venous thrombosis in mice. In the third aim we will also test the ability of therapeutics such as ADAMTS13 and a VWF-specific antibody to decrease thrombosis. These studies are important because they could help us better understand how inflammation associated with obesity influences VWF function and subsequently how this impacts thrombosis. This research may help improve treatment strategies for obese patients to lower their risk of thrombosis.