ABNORMAL EXPRESSION OF PLASMINOGEN-ACTIVATOR INHIBITORS IN PATIENTS WITH GESTATIONAL TROPHOBLASTIC DISEASE

We previously reported significantly elevated levels of plasminogen ac tivator inhibitor type I (PAI-1) in plasma and placenta from pregnant women with severe pre-eclampsia, and preeclampsia is a frequent proble m in molar pregnancies. As increases in PAI-1 may contribute to the pl acental alterations that occur in pre-eclampsia, we have begun to inve stigate changes in PAI-1 as well as PAI-2 and several other components of the fibrinolytic system in patients with trophoblastic disease. Si gnificant increases in plasma PAI-1 and decreases in plasma PAI-2 leve ls were observed in molar pregnancies when compared with the levels in normal pregnant women of similar gestational age, PAI-1 antigen level s also were increased and PAI-2 levels were decreased in placenta from women with molar pregnancies compared with placenta obtained by spont aneous abortion. lmmunohistochemical analysis revealed strong positive and specific staining of PAI-1 is trophoblastic epithelium in molar p regnancies and relatively weal staining of PAI-2. No association betwe en the distribution of PAI-1 and vitronectin was found, and no specifi c signal for tissue type PA, urokinase type PA, tumor necrosis factor- alpha, or interleukin-1 was detected, In situ hybridization revealed a n increase in PAI-1 but not PAI-2 mRNAs in placenta from molar pregnan cies in comparison with placenta from abortions. These results demonst rate increased PAI-1 protein and mRNA in trophoblastic disease and sug gest that localized elevated levels of PAI-1 may contribute to the hem ostatic problems associated with this disorder.