After a blood vessel in injured, platelets cluster together to plug the site of injury in the form of a blood clot (thrombus). In arterial disease, altered platelet aggregation can block blood vessels and cause heart attack or stroke.
Platelet aggregation involves the binding of many molecules to platelet integrin alpha-IIb beta 3, and blockade of this binding is effective in the prevention of blood clots.
However, chronic use of oral drugs that block alpha-IIb beta 3 activation have not proved beneficial in preventing recurrent blood clots.
In a study appearing online on July 12 in advance of publication in the August print issue of the Journal of Clinical Investigation, Mark Ginsberg and colleagues from the University of California San Diego show that the binding of the protein talin to alpha-IIb beta 3 is critical for integrin activation in mice, and that selective disruption of the talin-alpha-IIb beta 3 interaction protects mice from pulmonary thromboembolism - the formation of blood clots in the vessel that carries blood from the heart to the lungs.
Furthermore, this blockade results in very little pathological bleeding, which can often occur when the clotting process is disrupted.
The results suggest that modulation of the interaction between talin and alpha-IIb beta 3 could be an attractive strategy for the development of future anti-thrombotic drugs, with a reduced risk of pathological bleeding.