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
Journal of Clinical Investigation