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Scripps Research scientist discovers natural molecule indirectly prevents stable clot formation
Date:2/1/2011

LA JOLLA, CA January 31, 2011 A scientist from The Scripps Research Institute has identified a new role for a natural signaling molecule in preventing blood clot formation. The molecule could become a target for the development of novel and cost-effective treatments for blood clotting diseases such as Hemophilia A.

The findings, from a study by Scripps Research Assistant Professor Laurent O. Mosnier, were published in a recent edition of Journal of Biological Chemistry.

The study focused on Platelet Factor 4 a small cytokine (intracellular signaling molecule) released during platelet aggregation.

Based on Platelet Factor 4 effects on another coagulation protein, it was thought that Platelet Factor 4 could potentially stimulate activation of thrombin-activatable fibrinolysis inhibitor (TAFI) an enzyme (soluble protein) that protects clot longevity, making clots last longer and preventing excess bleeding; TAFI is like a hardener that is added to the mortar used between the bricks in a brick wall, without which the mortar would never completely solidify, and the wall would never be solid.

The new study, however, found exactly the opposite role for Platelet Factor 4inhibition of TAFI activation.

For Mosnier, this finding led to a radical ideasequestering Platelet Factor 4 using such molecules as heparin derivatives could improve clot stability. Heparin - a highly sulfated or negatively charged glucoseaminoglycan (polysaccharide or sugar derivative) is a commonly used anticoagulant. Mosnier, however, was able to modify the compound to have the reverse effect and aid in blood clotting in laboratory tests.

"The idea of using heparin to prevent bleeding in kids [who have bleeding tendencies] would be outrageous because that would just greatly accelerate bleeding," said Mosnier, "Our trick, however, was to modulate heparin's anticoagulant properties. This opens up new possibilities."

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Contact: Mika Ono
mikaono@scripps.edu
858-784-2052
Scripps Research Institute
Source:Eurekalert

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