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Friend or foe? How the body's clot-busting system speeds up atherosclerosis
Date:10/30/2008

Sometimes it's hard to tell friends from foes, biologically speaking. Naturally produced in the body, urokinase plasminogen activator and plasminogen interact to break up blood clots and recruit clean-up cells to clear away debris related to inflammation. In fact, urokinase manufactured as a drug effectively clears clogged arteries by generating clot-busting plasmin from blood-derived plasminogen.

However, despite the efficacy of urokinase and plasmin in clearing blood clots, evidence has shown that humans with a high baseline level of blood plasmin are at increased risk for heart attacks and for fast-developing forms of atherosclerosis. In addition, human arteries affected by atherosclerosis have an abundance of urokinase. These associations between plasmin, urokinase and increased atherosclerosis counter the notion that urokinase and plasmin protect against heart attacks by removing dangerous blood clots.

At first vascular biologists didn't know how to interpret these findings. Specifically, they wondered whether the high level of urokinase in atherosclerotic artery walls was contributing to atherosclerosis or was evidence of the body's efforts to fight it.

To try to resolve this puzzle, Dr. David A. Dichek, the John Locke Jr. Family Endowed Professor of Cardiology and associate director for research in the Division of Cardiology at the University of Washington (UW), and his team generated mice that were genetically engineered to produce more urokinase in their artery walls. These mice developed arteries with worse atherosclerosis, including thicker walls, narrower interiors, and limited blood flow. The mice died suddenly with clogged arteries and evidence of heart attacks.

Dichek noted other reasons why his team expected that increased activity of the urokinase/plasminogen system would promote atherosclerosis, including the roles of urokinase and plasminogen in inflammation and cell migration.

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Contact: Leila Gray
206-685-0381
University of Washington
Source:Eurekalert

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