Project 171709

Heart attacks and strokes are often caused by a series of events starting with the disruption of fatty plaques on the inner lining of blood vessel arteries. Subsequently, one of the main events is the clumping of tiny cells termed platelets along the exposed plaque within a blood vessel artery that supplies blood and oxygen to either the heart or brain. Platelets are required for the normal stoppage of blood flow when cuts and injuries occur. However, when they clump together in an uncontrolled manner within an artery the consequences can be devastating. There are two proteins COX-1 and COX-2 within the human body that control the production of two fat-derived molecules known as thromboxane and prostacyclin. These substances regulate how platelets clump together. We do not know exactly where and when COX-2 is found within blood vessels and during the process when platelets are made. We will study a specially designed mouse with a fluorescent COX-2 protein to examine where it is found. Novel mouse strains in which the two COX forms are exchanged will also allow us to investigate how the two proteins function to control platelet clumping when a blood vessel is injured. A special microscope technique can be used to visualize blood vessels in live mice and to follow the developing clump of platelets (thrombus). We will use innovative techniques (gene and cell therapy) to deliver prostacyclin so as to prevent or limit the damage when a thrombus forms. This research is important because it will help us to understand the basic mechanisms of thrombus formation and how the two COX proteins function, which may lead to new treatments for cardiovascular disease.