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Atherosclerotic Plaque Rupture Linked To Cell Enzyme

Release and activation required for effect, and both may be treatment targets

FRIDAY, Dec. 23 (HealthDay News) -- The expression of an active form of the enzyme MMP-9 in mice with atherosclerosis appears to trigger plaque rupture that can lead to heart attack or stroke, according to a study in the Dec. 22 online edition of the Journal of Clinical Investigation.

Elaine Raines, Ph.D., of the University of Washington in Seattle, and colleagues overexpressed matrix metalloproteinase-9 (MMP-9) in the macrophages of advanced atherosclerotic lesions in mice. It has been previously suggested that macrophages play a key role in inducing plaque rupture as rupture-prone lesions have been shown to be macrophage-rich.

The investigators found that macrophages secreting an autoactivating form of MMP-9 enhanced elastin breakdown in the surrounding extracellular matrix that physically stabilizes the plaque, and consequently induced plaque rupture.

"These data show that enhanced macrophage proteolytic activity can induce acute plaque disruption and highlight MMP-9 as a potential therapeutic target for stabilizing rupture-prone plaques," the authors conclude.

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