Induction of type 1 plasminogen activator inhibitor in human liver ischemia and reperfusion

Abstract 

Background/Aims: The detailed role of type 1 plasminogen activator inhibitor (PAI-1) in liver with ischemia reperfusion injury remains unclear. The aim of the present study was to examine this mechanism, focusing on inflammatory cytokines.

Methods: Eighteen patients who underwent partial hepatectomy (PH) for metastatic liver tumors using only Pringle's maneuver were enrolled in the study. Peripheral blood was taken perioperatively and PAI-1, tissue type plasminogen activator (tPA), plasma aspartate aminotransferase (AST) and cytokine levels were measured. Two liver specimens were taken from each patient, one before ischemia and the other after PH, for detection of mRNA of PAI-1, tPA, tumor growth factor (TGF)-β1, interleukin-1β and tumor necrosis factor-α. Immunohistochemistry and Western blotting were performed to detect PAI-1 protein in the liver.

Results: The average plasma PAI-1 antigen level reached a maximum after the final clamp (121.6±5.9 ng/ml). The average PAI-1 level in hepatic veins (140.4±6.3 ng/ml) after the last Pringle's maneuver was higher than that in peripheral veins (p<0.0001). A correlation was observed between the ratio of the corrected fluorescent activity of PAI-1 before and after ischemia and TGF-β1 mRNA levels in the liver after PH (p=0.003). PAI-1 protein could be detected in parenchymal and non-parenchymal cells of the liver obtained after ischemia reperfusion injury.

Conclusions: PAI-1 was produced in human livers after ischemia reperfusion injury provoked by Pringle's maneuver, giving valuable information regarding the degree of warm ischemic damage.

Keywords:  Ischemia/reperfusion injury, Plasminogen activator inhibitor, Tumor growth factor β1