Key result
PAI-1 inhibition fails to improve cardiac function or reduce infarct size after myocardial ischemia/reperfusion.
Why the study?
Plasminogen activator inhibitor-1 (PAI-1) contributes to cardiac ventricular remodeling, but its roles in myocardial ischemia reperfusion (I/R) injury and the subsequent inflammatory response had not been well elucidated.
Answers are grounded in this paper and cite their sources.
Demonstrates that pharmacological inhibition of plasminogen activator inhibitor-1 does not alter ventricular remodeling after ischemia reperfusion in rats, suggesting limited therapeutic utility.
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.
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Watanabe et al. (2011) studied Myocardial ischemia/reperfusion injury (rat model) (n=39). IMD-1622 (specific PAI-1 inhibitor) vs. Vehicle was evaluated on Ventricular remodeling and cardiac function after myocardial ischemia/reperfusion injury (fractional shortening, infarct size/area at risk ratio, and interstitial fibrosis) (p=NS). Pharmacological PAI-1 inhibition with IMD-1622 (20 mg/kg) did not significantly improve fractional shortening, infarct size, or interstitial fibrosis compared to vehicle in rats after myocardial I/R.
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