Coronary artery disease (CAD) and transplant associated-CAD are caused by a reduction or complete blockage of blood flow in blood vessels of the heart, which results in tissue death due to lack of oxygen. CAD is the leading cause of heart attacks, and transplant associated-CAD is the leading cause of organ failure one year after transplantation. Both diseases are characterized by abnormalities in blood vessel walls – abnormalities that result in the accumulaton of lipids and other blood components inside vessel walls. This causes them to thicken which acts to constrict blood flow. The endothelium is a blood vessel lining that serves as a barrier between the blood and tissue and also has a role in directing the transport of ions, lipids and proteins. Previous research has shown that vascular endothelial growth factor (VEGF), one of the most potent inducers of vascular permeability, is upregulated in these diseases. Brian Wong is working to determine the specific mechanisms by which VEGF induces this effect. He hypothesizes that the abnormal production of VEGF in CAD and transplant associated-CAD compromises endothelial barrier function, resulting in the increased passage of lipids and proteins into the vessel wall. Ultimately, he hopes to determine the therapeutic potential of blocking VEGF production in order to reduce lipid entry and accumulation in the vessel wall and prevent these diseases.