Effects of Pharmacological Suppression of Plasminogen Activator Inhibitor-1 in Myocardial Remodeling After Ischemia Reperfusion Injury

概要

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Plasminogen activator inhibitor-1 (PAI-1) contributes to cardiac ventricular remodeling because migration of inflammatory cells and attenuation of extracellular matrix degradation are caused by plasmin and matrix metalloproteinase. However, the roles of PAI-1 in myocardial ischemia reperfusion (I/R) injury and the following inflammatory response have not yet been well elucidated. To clarify the role of PAI-1 in myocardial I/R injury, we used a specific PAI-1 inhibitor (IMD-1622) in a rat model. The left anterior descending coronary artery was ligated and reperfusion was performed by loosening the suture after 30 minutes of arterial occlusion. A single administration of IMD-1622 (20 mg/kg) or vehicle was given intraperitoneally and then the rats were sacrificed on day 1 or day 14 after I/R. Blood pressure, echocardiograms, histopathology, and molecular examination were performed. The examinations revealed that PAI-1 inhibitor showed limited effects on cardiac dysfunction and ventricular remodeling after I/R. We conclude that the pharmacological inhibition of PAI-1 may not affect ventricular remodeling after myocardial I/R injury.