Enzyme triggers plaque rupture in hardened arteries, causing heart attack and stroke

University of Washington researchers have revealed that, in mice with atherosclerosis, it is the expression of an active form of the enzyme MMP-9, by macrophages located within plaque buildup in narrowed coronary arteries, that triggers plaque rupture. This rupture can cause blood clots and block blood flow to the heart and brain, causing a heart attack or stroke. The results appear online on December 22 in advance of print publication in the January 2006 issue of the Journal of Clinical Investigation.

Atherosclerosis involves the slow buildup of fatty substances, cholesterol, collagen and elastin fibers, macrophages, and other molecules in the arterial lining, which results in formation of a plaque that can partially or totally block the flow of blood. 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.

Elaine Raines and colleagues devised a strategy to overexpress matrix metalloproteinase-9 (MMP-9) in the macrophages of advanced atherosclerotic lesions in mice. The authors 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. MMP-9 and factors that regulate its activation may be potential therapeutic targets for stabilizing rupture-prone plaques.

TITLE: Macrophage expression of active MMP-9 induces acute plaque disruption in apoE-deficient mice

AUTHOR CONTACT:
Elaine Raines
University of Washington, Seattle, Washington, USA
Phone: 206-341-5410; Fax: 206-341-5416; E-mail: ewraines@u.washington.edu

View the PDF of this article at: https://www.the-jci.org/article.php?id=25074

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