A Plasminogen Activator Inhibitor (PAI-2) Circulates in Two Molecular Forms During Pregnancy

Abstract

During normal pregnancy maternal haemostasis alters to protect against bleeding with a rise in plasma clotting factor levels and increased inhibition of fibrinolysis. The latter is due in part to increased levels of the 48 kDa plasminogen activator inhibitor (PAI-1) present in the plasma of non-pregnant individuals. A second plasminogen activator inhibitor (PAI-2) occurs in placenta and in a cultured histiocytic lymphoma cell line. We report here the identification by SDS-PAGE and zymography of PAI-2 in plasma during normal pregnancy. PAI-2 was present in two molecular forms of about 75 and 130 kDa, which were detectable at 12 weeks gestation and which persisted in the maternal circulation for up to 7 days after delivery. These forms of PAI-2 appear to be distinct from purified PAI-2, which has a molecular mass of 47-60 kDa and which is not normally detectable in this zymographic system, since it is sensitive to denaturants. The novel forms of PAI-2 may represent complexes or aggregates that retain activity after SDS-PAGE.