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Dangerous plaques in blood vessels rupture by overproducing protein-busting enzymes
Date:3/29/2010

essels called plasminogen and turns it into plasmin, another protein-destroying enzyme. In several studies, patients whose blood tests showed a high level of plasminogen activation had an elevated risk of future heart attacks and strokes. The new mouse study, the researchers noted, helps explain this somewhat puzzling clinical finding. Their data suggests that high levels of urokinase in plaque, leading to increases in plasminogen activation, may be causally related to plaque rupture and major cardiovascular events.

An improved understanding of the underlying cellular and molecular mechanisms that cause plaques to rupture puts medical scientists in a better position to develop preventive approaches and more effective treatments for vulnerable plaque

"Our findings point to both diagnostic and therapeutic strategies," Dichek noted. "We eventually may be able to identify patients who are more at risk for heart attacks and strokes than are others. At present this is very difficult to do simply by imaging plaques. We might find ways to prevent plaque rupture in these high- risk patients and thereby prevent many life-threatening or disabling cardiovascular events."

Perhaps, he said, this would be through interventions that decrease production of protein-destroying enzymes in the artery wall or that block their activities. A caveat for this approach would be taking steps to avoid toxicity to the patient.

"On the other hand, if we discover that a specific MMP enzyme is found only this disease state, it would make an ideal treatment target," Dichek added. Other options might be transferring genes into the blood vessel wall to lessen the manufacture of protein-digesting enzymes.

"But we have quite a long way to go before developing an effective gene transfer method and making it practical," he said.

However, he added, "I hope it might eventually be possible to transform atherosclerosis into a condition that like grey hai
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Contact: Leila Gray
leilag@u.washington.edu
206-685-0381
University of Washington
Source:Eurekalert  

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