New molecular target found to reduce clotting without excessive bleeding

Washington, Sept 27: According to a new study a new molecular target in blood clot formation has been found which may help to reduce clotting without any excessive bleeding.

unveils a new molecular target for anti-platelet drugs, which may avoid the dangerous side-effects of the current drugs."

The study, led by Shafi Kuchay and Dr. Athar Chishti, was made at the University of Illinois at Chicago College of Medicine.

"It was very surprising to find an enzyme whose inhibition lessened platelet aggregation without abnormal bleeding, and we immediately realized that it could have very important implications for the treatment of cardiovascular disease," Shafi Kuchay said.

When clots are formed, small blood cells called platelets begin to bundle up.

The risk of heart attack and stroke is reduced by, aspirin and other anti-clotting agents by blocking the biochemical pathway which causes platelets to become sticky.

However, all these drugs put patients at risk of excessive bleeding which is one of the most common side-effect of anti-clotting agents.

The researchers made a mouse model to conduct the study. The mice lacked a gene, protease enzyme, which is most commonly found in blood cells called calpain-1, were studied to determine its function.

They discovered that mice lacking calpain-1 had reduced platelet aggregation but did not have any abnormal bleeding. The mice lacking calpain-1 called "knockout" mice had increased levels of another enzyme, known as protein tyrosine phosphatase-1B.

Later, when the mice were given a PTP1B inhibitor, the reduced platelet aggregation was restored. When calpain-1 knockout mice and mice lacking PTP1B were crossed in order to create double-knockout mice, platelet aggregation was restored in the offspring that lacked the genes for both enzymes.

The researchers were therefore established that PTP1B turns off the signal for platelet aggregation and that calpain-1 regulated the amount and activity of this "off switch."

"Because of the danger of excessive bleeding, people taking anti-clotting medications are monitored carefully and warned not to exceed their recommended doses. Our research unveils a new molecular target for anti-platelet drugs, which may avoid the dangerous side-effects of the current drugs." Dr. Athar Chishti

The findings are reported in Molecular and Cellular Biology. (With inputs from ANI)

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