Better understanding of clotting dynamics in atherosclerosis could lead to more effective drugs

Published on November 8, 2012 at 6:55 AM · No Comments

To investigate this alteration, the researchers used an intracellular fluorescent dye that binds to calcium. They found that when the flow stops, the platelets' calcium levels increase and they become activated. By adding drugs that block ADP and thromboxane, chemicals involved in the clotting process, the researchers were able to prevent this platelet calcium mobilization and stop the contraction.

Millions of patients already take drugs that target these chemical pathways: P2Y12 inhibitors, such as Plavix, block ADP signaling in platelets, and aspirin blocks platelets' synthesis of thromboxane. This discovery suggests that these drugs may be interfering with contractile mechanisms that are triggered when ADP and thromboxane become elevated, such as when the flow around the clot decreases or stops. Beyond slowing the growth of clots, these anti-platelet drugs may also be altering the mechanics of the clot by preventing contraction.

"It is an example of 'quorum sensing' by the platelets in the clots," Diamond said. "The platelets are sensing each other and the prevailing environment. This causes them to release ADP and thromboxane, but it is rapidly diluted away by the surrounding blood flow.

"However, when the flow over the clot decreases or stops, the ADP and thromboxane levels rapidly build up, and this drives platelet contraction," Diamond said.

The research was supported by the National Institutes of Health.

Source: University of Pennsylvania

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