Polyphosphate from blood platelets plays a key role in inflammation and the formation of blood clots, scientists from the Swedish medical university Karolinska Institutet have shown. The study, which is presented in the scientific journal Cell, describes how this mechanism can be used in treatment.
Blood clots are a common cause of myocardial infarction and stroke, and they arise when blood coagulates and clogs a blood vessel. Scientists have shown that the formation of a blood clot involves the aggregation of blood platelets and the formation of structures known as "fibrin threads," in combination with inflammation in the blood vessel. The molecular processes behind this, however, are only partially known.
A research group at Karolinska Institutet, in collaboration with American and European scientists, has discovered that an inorganic polymer, polyphosphate, plays a key role in both inflammation and the formation of blood clots. Experiments on mice and with patient plasma have shown that polyphosphate is released by blood platelets and activates Factor XII, a protein that scientists have previously shown to contribute to coagulation. Polyphosphate also activates inflammatory substances that contribute to leakage from the blood vessel, which is a characteristic feature of inflammation.
The scientists show also that certain enzymes, phosphatases, that break down polyphosphate can prevent both inflammation and the formation of blood clots in the blood vessels of mice. Thus the scientists believe that phosphatases can become the focus for a new type of treatment for blood clots and inflammation.
The discovery opens up opportunities for drug development, according to Dr Nicola Mutch from the University of Leeds who carried out the UK branch of the research.
"The challenge in designing treatments to reduce thrombosis is getting the balance right. We need to find an appropriate drug level or target which causes enough anticoagulation to prevent risk of heart attack or stroke but with minimal bleeding side effects," she explains.
"Our work suggests polyphosphate or factor XII could be potential new targets, as neither seems to affect our ability to heal naturally, so drugs based on these molecules could offer a major improvement on existing treatments."
- Felicitas Mόller, Nicola J. Mutch, Wolfdieter A. Schenk, Stephanie A. Smith, Lucie Esterl, Henri M. Spronk, Stefan Schmidbauer, William A. Gahl, James H. Morrissey, and Thomas Rennι. Platelet Polyphosphates Are Proinflammatory and Procoagulant Mediators In Vivo. Cell, Online 10 December 2009
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