Helping anti-clotting drugs work better

Control of thrombosis by endogenous pathways of platelet inhibition and relevance to anti-platelet therapy

Professor Timothy Warner wants to understand how anti-clotting medicines work to find new ways to prevent heart and circulatory disease. In atherosclerosis, the underlying cause of coronary heart disease, the coronary arteries fur up with fatty plaques and narrow. If the fatty plaque ruptures, a blood clot can form in the artery, blocking off the blood supply and causing a heart attack or a stroke. Many people at risk of coronary heart disease are given anti-clotting drugs to protect them, and the target of these drugs is the blood platelets, which stick together to form blood clots. Platelet activity is tightly controlled. Endothelial cells in blood vessel walls release anti-clotting molecules called nitric oxide (NO) and prostaglandin I2 (PGI2) that constantly bathe the circulating platelets. But PGI2 and NO levels decline in people with diseases such as high blood pressure, atherosclerosis and diabetes, so they are more dependent on anti-clotting medicines to protect them. Professor Warner has found NO and PGI2 do not work as effectively when blood clots form. He has also discovered that one class of anti-clotting drug amplifies the effects of NO and PGI2 by blocking proteins on the platelet cell surface called P2Y12 receptors. In this project, Professor Warner will study how P2Y12 receptor blockers work together with the body's own PGI2 and NO to prevent blood clots. A better understanding of how anti-platelet drugs work with the body’s own anti-clotting molecules could reveal new ways to prevent blood clotting and heart disease.