Novel Inhibitors of Thrombotic Clot Formation

The Rockefeller University
posted on 01/26/2010

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The human body has many mechanisms to combat infection and injury in order to maintain a healthy state. One mechanism in particular is the formation of blood clots, which helps us to heal from wounds quickly and prevent infection. However, blood clot formation can be lethal if it occurs in the wrong place. The single most common cause of morbidity and mortality in the United States is arterial thrombosis, which is the formation of blood clots in the major blood vessels that block the blood supply to vital parts of the body, including the brain and the heart. These clots form because the body perceives that the blood vessels are injured, either due to atherosclerotic plaques or surgical procedures such as angioplasty or stent placements. The clots themselves are composed of fibrin and platelets, which are small cellular fragments in the blood that aggregate by binding a protein called fibrinogen. It is thus important to identify compounds that inhibit platelets from forming these clots. Our investigators have used high-throughput screening methods to discover novel compounds that inhibit or reduce the binding of platelets to fibrinogen and the aggregation of platelets, thus potentially preventing the formation of the clots. Research is ongoing to optimize and characterize the compounds' specific biological activity in vitro and in vivo.