Abnormal expression of plasminogen activator inhibitors in patients with gestational trophoblastic disease.
We previously reported significantly elevated levels of plasminogen activator inhibitor type 1 (PAI-1) in plasma and placenta from pregnant women with severe pre-eclampsia, and pre-eclampsia is a frequent problem in molar pregnancies. As increases in PAI-1 may contribute to the placental alterations that occur in pre-eclampsia, we have begun to investigate changes in PAI-1 as well as PAI-2 and several other components of the fibrinolytic system in patients with trophoblastic disease. Significant increases in plasma PAI-1 and decreases in plasma PAI-2 levels were observed in molar pregnancies when compared with the levels in normal pregnant women of similar gestational age. PAI-1 antigen levels also were increased, and PAI-2 levels were decreased in placenta from women with molar pregnancies compared with placenta obtained by spontaneous abortion. Immunohistochemical analysis revealed strong positive and specific staining of PAI-1 in trophoblastic epithelium in molar pregnancies and relatively weak staining of PAI-2. No association between the distribution of PAI-1 and vitronectin was found, and no specific signal for tissue type PA, urokinase type PA, tumor necrosis factor-alpha, or interleukin-1 was detected. In situ hybridization revealed an increase in PAI-1 but not PAI-2 mRNAs in placenta from molar pregnancies in comparison with placenta from abortions. These results demonstrate increased PAI-1 protein and mRNA in trophoblastic disease and suggest that localized elevated levels of PAI-1 may contribute to the hemostatic problems associated with this disorder.
Estellés
A
A
Centro de Investigatiõn, Hospital Universitario La Fe, Valencia, Spain.
Grancha
S
S
Gilabert
J
J
Thinnes
T
T
Chirivella
M
M
España
F
F
Aznar
J
J
Loskutoff
D J
DJ
D005260:Female; D006801:Humans; D006828:Hydatidiform Mole / Q000097:blood* / Q000737:chemistry*; D010920:Placenta / Q000737:chemistry; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis / Q000097:blood; D017396:Plasminogen Activator Inhibitor 2 / Q000032:analysis / Q000097:blood; D015849:Plasminogen Inactivators / Q000032:analysis* / Q000097:blood; D011247:Pregnancy; D019396:Tissue Polypeptide Antigen / Q000032:analysis / Q000097:blood; D014594:Uterine Neoplasms / Q000097:blood* / Q000737:chemistry*
D017395:Plasminogen Activator Inhibitor 1; D017396:Plasminogen Activator Inhibitor 2; D015849:Plasminogen Inactivators; D019396:Tissue Polypeptide Antigen