Disruption of the plasminogen gene in mice abolishes wound healing after myocardial infarction

The plasminogen system plays an important role in the proteolytic degradati on of extracellular matrices during wound healing. In the present study we investigated the impact of the plasminogen system on cardiac wound healing and function after myocardial infarction, Myocardial infarction was induced in plasminogen-deficient mice (Plg-/-) and in wild-type controls (Plg+/+), Structural analysis 1, 2, and 5 weeks after infarction revealed that infar ct healing was virtually abolished in Plg-/- mice, indicating that the plas minogen system is required for the repair process of the heart after infarc tion. In the absence of plasminogen, Inflammatory cells did not migrate int o the infarcted myocardium, Necrotic cardiomyocytes were not removed and th e formation of granulation tissue and fibrous tissue did not occur. In thes e nonhealing infarcted hearts, LV dilatation was not altered, In addition, gelatinolytic activity of MMP-2 and MMP-9 was depressed in the Plg-/- infar cted hearts, suggesting that the plasmin effect on infarct healing may be m ediated by MMPs. Surprisingly, cardiac function was only attenuated to a ra ther small extent in the Plg-/- infarcted mice when compared to the wild-ty pes. This study provides direct prove that plasmin-mediated proteolysis pla ys a central role in cardiac wound healing after myocardial infarction in m ice.