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Scripps Research team sheds new light on how blood clots form
Date:6/13/2011

Scripps Research Institute scientists have discovered new elements of the blood clot-formation process. The findings could lead to better drugs for preventing heart attacks and other clot-related conditions.

The work, which was published by the Journal of Clinical Investigation in an advance, online edition June 13, 2011, helps to establish a new model of clot formation.

According to the old model, an injury to the wall of blood vessels causes smooth muscle cells to expose a clot-organizing protein called tissue factor. "In the emerging new model, tissue factor exists on the surfaces of these smooth muscle cells, as well as on circulating immune cells, but in an inactive state," said Scripps Research Professor Wolfram Ruf. "In this study, we've shown that cell-surface receptor P2X7, which was known to promote inflammation when stimulated, also plays a major role in the clot-forming process by activating tissue factor."

An Intriguing Target

To better understand clot formation, Ruf and his colleagues performed a set of experiments on cultured mouse cells and transgenic mouse models. The team's investigation began with the P2X7 receptor, because of its known role in the inflammatory response that can lead to excessive clotting in sepsis, a severe illness in which the bloodstream is overwhelmed by bacteria.

Normally, when cells are damaged, they release large quantities of energy-storage molecules known as adenosine triphosphate (ATP). Previous research had hinted that when this freed ATP encounters passing immune cells, it serves as a damage signal, stimulating the immune cells' P2X7 receptors and causing the release of "microparticles" exposing the clot-promoting tissue factor. The new study showed that ATP can affect P2X7 receptors on both immune cells and smooth muscle cells.

To confirm the significance of the P2X7 receptor in the clot-forming process, the team bred transgenic mice that lacked
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Contact: Mika Ono
mikaono@scripps.edu
858-784-2052
Scripps Research Institute
Source:Eurekalert

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