Plasminogen Activator Inhibitor-1 Is the Primary Inhibitor of Tissue-Type Plasminogen Activator in Pregnancy Plasma

Maja Jørgensen; Malou Philips; Sixtus Thorsen; Johan Selmer; Jesper Zeuthen

doi:10.1055/s-0038-1646006

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1987; 58(03): 872-878
DOI: 10.1055/s-0038-1646006

Original Article

Schattauer GmbH Stuttgart

Plasminogen Activator Inhibitor-1 Is the Primary Inhibitor of Tissue-Type Plasminogen Activator in Pregnancy Plasma

Maja Jørgensen

¹The Department of Clinical Chemistry, University of Copenhagen, Hvidovre Hospital, Hvidovre, Denmark

,

Malou Philips

¹The Department of Clinical Chemistry, University of Copenhagen, Hvidovre Hospital, Hvidovre, Denmark

,

Sixtus Thorsen

¹The Department of Clinical Chemistry, University of Copenhagen, Hvidovre Hospital, Hvidovre, Denmark

,

Johan Selmer

²The NOVO BioLabs, Novo Industri A/S, Bagsværd, Denmark

,

Jesper Zeuthen

²The NOVO BioLabs, Novo Industri A/S, Bagsværd, Denmark

› Author Affiliations

Abstract

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Summary

The aim of the present work was to clarify to what extent plasminogen activator inhibitor-1 (PAI-1) and plasminogen activator inhibitor-2 (PAI-2) contribute to the increase in plasma inhibition of tissue-type plasminogen activator (t-PA) observed during pregnancy. It was demonstrated that a monoclonal antibody against PAI-1 almost completely quenched inhibition of single-chain t-PA and most of the inhibition of two-chain t-PA in plasma during the third trimester of piegnancy. The remaining inhibition of two-chain t-PA was to a great extent abolished by a PAI-2 antibody. The second order rate constant (k₁) for inhibition of single-chain t-PA by the inhibitor neutralized by the PAI-1 antibody was about 4.8 · 10⁶ M^-1 · s^-1. The conversion of singlechain t-PA to the two-ehain form increased the reaction rate with the inhibitor about 3-fold. These kinetic data are compaiable with those obtained with TAI-l in non-pregnancy plasma oi with purified PAI-1. From the above results it is concluded that PAI-1 is the primary inhibitor of both single-chain and two chain t PA and that PAI-2 is the secondary inhibitor of two-chain t-PA in pregnancy plasma. The concentration of reactive PAI-1 versus gestation age was assayed in plasma from 6 women by binding of PAI-1 to ¹²⁵I-labelled single-chain t-PA followed by quantitation of the labelled t-PA-PAI-1 complex after separation by SDS- polyacrylamide gel electrophoresis. It was found that the concentration of PAI-1 increased 4 to 8-fold during the gestation period reaching a level of about 1.4 nM at term. Post partum the plasma concentration declined abruptly within 24 h to the level observed in age-matched non-pregnant women.

Keywords

Plasma - Plasminogen activator inhibitor-1 - Plasminogen activator inhibitor-2 - Pregnancy - Tissue-type plasminogen activator

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References

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