ABNORMAL EXPRESSION OF TYPE-1 PLASMINOGEN-ACTIVATOR INHIBITOR AND TISSUE FACTOR IN SEVERE PREECLAMPSIA

Preeclampsia is a multisystemic obstetric disease of unknown etiology that is commonly associated with fibrin deposition, occlusive lesions in placental vasculature, and intrauterine fetal growth retardation. W e previously reported that type 1 plasminogen activator inhibitor (PAI -1) levels are significantly increased in plasma and placenta from pre gnant women with preeclampsia compared to normal pregnant women. In th e present report we localize the expression of placental PAI-1 in grea ter detail and compare it with that of tissue factor (TF), a procoagul ant molecule, and vitronectin (Vn), a PAI-1 cofactor. We also examine the expression of two cytokines, tumor necrosis factor alpha (TNF alph a) and interleukin-1 (IL-1), in order to begin to define the underlyin g mechanisms responsible for the elevated levels of PAI-I and fibrin d eposits observed in placenta from preeclampsia. We demonstrate a signi ficant increase in PAI-1, TF and TNF alpha antigen and PAI-1 and TF mR NA in placentas from preeclamptic patients. PAI-1 mRNA was increased n ot only in syncytiotrophoblast and infarction areas, but also in fibro blasts and in some endothelial cells of fetal vessels in placentas fro m preeclamptic patients. However, there was no colocalization between PAI-I, TF, Vn and TNF alpha. in placental villi. The elevated TNF alph a in the placenta may induce PAI-I and TF, and thus promote the thromb otic alterations associated with preeclampsia.