Summary
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. We previously reported that type 1 plasminogen
activator inhibitor (PAI-1) levels are significantly increased in plasma and placenta
from pregnant women with preeclampsia compared to normal pregnant women. In the present
report we localize the expression of placental PAI-1 in greater detail and compare
it with that of tissue factor (TF), a procoagulant molecule, and vitronectin (Vn),
a PAI-1 cofactor. We also examine the expression of two cytokines, tumor necrosis
factor α (TNFα) and interleukin-1 (IL-1), in order to begin to define the underlying
mechanisms responsible for the elevated levels of PAI-1 and fibrin deposits observed
in placenta from preeclampsia. We demonstrate a significant increase in PAI-1, TF
and TNFα antigen and PAI-1 and TF mRNA in placentas from preeclamptic patients. PAI-1
mRNA was increased not only in syncytiotrophoblast and infarction areas, but also
in fibroblasts and in some endothelial cells of fetal vessels in placentas from preeclamptic
patients. However, there was no colocalization between PAI-1, TF, Vn and TNFα in placental
villi. The elevated TNFα in the placenta may induce PAI-1 and TF, and thus promote
the thrombotic alterations associated with preeclampsia.