Enzyme Triggers Plaque Rupture In Hardened Arteries, Causing Heart Attack And Stroke

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.