Overexpression of Urokinase by Plaque Macrophages Causes Histological Features of Plaque Rupture and Increases Vascular Matrix Metalloproteinase Activity in Aged Apolipoprotein E–Null Mice

Abstract

In advanced plaques of Apoe(-/-) mice, macrophage uPA overexpression causes intraplaque hemorrhage and fibrous cap disruption, features associated with human plaque rupture. uPA overexpression also increases vascular matrix metalloproteinase activity. These data provide a mechanism that connects macrophage uPA expression, matrix metalloproteinase activity, and plaque rupture features in mice. The data also suggest that elevated plaque plasminogen activator expression and plasminogen activation in humans may be causally linked to plaque rupture and cardiovascular events.