Gene offers clues to new treatments for a harmful blood clotting disorder

UNIVERSITY PARK, Pa. -- A gene associated with both protection against bacterial infection and excessive blood clotting could offer new insights into treatment strategies for deep-vein thrombosis -- the formation of a harmful clot in a deep vein, according to a new research discovery to be published by a team led by a Penn State scientist and his colleague at Harvard University. The gene produces an enzyme that, if controlled via a specific drug therapy, could offer hope to patients prone to deep-vein clots, such as those that sometimes form in the legs during lengthy airplane flights or during recuperation after major surgery. When blood clots form within deep veins, the clots can travel to the heart, causing cardiac arrest or to the lungs, causing breathing problems.

The leaders of the research team are Yanming Wang, a Penn State associate professor of biochemistry and molecular biology, and Denisa Wagner, senior author with decades of research on thrombosis at the Boston Children's Hospital and the Harvard University Medical School. With studies of mice, the scientists discovered that the enzyme produced by the gene, named PAD4, plays a critical role in the formation of a blood clot, as well as in the formation of a bacteria-killing web named NET (neutrophil extracellular trap).

Wang said his team's experiments show clearly that the PAD4 enzyme plays a critical role in the formation of a blood clot, as well as in the formation of a bacteria-fighting NET. "PAD4, which is also called PADI4 in humans, is a necessary enzyme involved in multiple disorders," Wang said. "On the one hand, it plays an integral part in the body's defense system. On the other hand this enzyme acts to silence tumor-suppressor genes. Now, we are starting to see that its overactivity also may be part of the reason that some individuals suffer from deep-vein clotting."

Wang added that patients prone to deep-vein thrombosis might benefit from drugs that target the PAD4 enzyme. "In future research, specific drug therapies could be developed and tested with the goal of targeting this enzyme. "If we could find a way to dial back the enzyme's clot-forming effects, we might be able to offer new hope to patients suffering from clotting disorders and deep-vein thrombosis."

More information is online at http://www.science.psu.edu/news-and-events/2013-news/Wang5-2013.

The research was funded by the National Heart, Lung and Blood Institute of the National Institutes of Health and the National Cancer Institute.

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Last Updated May 14, 2013