PAI-1 is a serine protein inhibitor that is secreted in response to inflammatory reactions.

PAI-1 is the main inhibitor of tissue-type plasminogen activator (tPA) and urokinase plasminogen activator (uPA) and, as such, plays an important role in the regulation of fibrinolysis.

Plasminogen Activator Inhibitor (PAI-1) AG is useful to:

- aid in prognosis of occurrence or recurrence of thrombosis

- intentify heredity elevation or deficiency of plasminogen activator inhibitor type 1.

- determine the risk for veno-occlusive disease associated with bone marrow transplantation.

- aid diagnosis of impaired fibrinolysis

The plasminogen activator system plays a key role in a wide range of physiological and pathological processes, including coagulation, fibrinolysis, inflammation, wound healing, and malignancy. A crucial reaction of the plasminogen activator system is the conversion of plasminogen to plasmin by plasminogen activators.

Plasminogen activator inhibitor-1 (PAI-1) is a member of the superfamily of serine-protease inhibitors (or serpins), and the principal inhibitor of both the tissue-type and the urinary-type plasminogen activator, the two plasminogen activators able to activate plasminogen.

The main enzyme of the plasminogen activator system is plasmin. Plasmin is a serine protease playing a key role in the fibrinolysis cascade being responsible for the final degradation of fibrin and extracellular matrix proteins. Plasmin is similar to trypsin, and is generated from its precursor plasminogen by the plasminogen activators.

Plasminogen is primarily present in the plasma, and the liver represents its primary site of synthesis. However, plasminogen mRNA has been found in several mouse tissues, including adrenal, kidney, brain, testis, heart, lung, uterus, spleen, thymus, and gut, supporting the broad functional role played by the plasminogen activator system. The activation of plasminogen into plasmin is mediated by two types of activators, urokinase-type plasminogen activator (u-PA) and tissue-type plasminogen activator (t-PA).

The activity of both is regulated by specific plasminogen activator inhibitors (PAIs). The principal PAIs are PAI type 1 (PAI-1), initially called the endothelial cell PAI, PAI type 2 (PAI-2), also known as placental-type PAI, and PAI type 3 (PAI-3), which is identical to protein C inhibitor.

Among the inhibitory factors, the rapid acting PAI-1 is one of the most important inhibitors of the plasma fibrinolytic activity. PAI-1 is a single chain glycoprotein member of the superfamily of serine-protease inhibitors (or serpins). It is composed by 379 aminoacids with an apparent molecular weight of 48 kDa. PAI-1 (or serpin E1) is the principal inhibitor of both the tissue-type plasminogen activator (t-PA) and the urinary-type plasminogen activator (u-PA), which are able to activate plasminogen by cleaving a specific Arg-Val peptide bond located within the protease domain. Differently from t-PA (which is mainly involved in intravascular fibrinolysis), u-PA exerts proteolytic effects as well as intracellular signaling functions by binding to its high affinity receptor on the cell surface.

Notes:

- The plasminogen activator inhibitor type 1 (PAI-1) level shows a diurnal variation with the highest levels occurring in the morning.

- The PAI-1 level increases during pregnancy and decreases rapidly after delivery.

- The extremely rare presence of antimouse antibodies in certain patients may lead to anomalous results.

- Inappropriate specimen collection and processing may lead to platelet activation and release of platelet PAI-1. Consequently, care must be taken to remove all platelets and minimize platelet activation during specimen collection and processing.

References:

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