Plasminogen activator inhibitor-1

Plasminogen activator inhibitor-1 (PAI-1) is a protein that in humans is encoded by the SERPINE1 gene. It is a member of the serpin superfamily of proteins, which function as serine protease inhibitors. PAI-1 is the primary inhibitor of tissue plasminogen activator (tPA) and urokinase (uPA), the activators of plasminogen and hence fibrinolysis.

Function

PAI-1 inhibits the tissue plasminogen activator and urokinase, which are involved in fibrinolysis, the physiological process that degrades blood clots. The high concentration of PAI-1 is thought to contribute to thrombosis, as it can inhibit the breakdown of clots.

Clinical significance

Elevated levels of PAI-1 have been linked to an increased risk of thrombosis and a number of other diseases, including cardiovascular disease, stroke, and diabetes. It is also involved in cell adhesion and migration, which has implications for tumor growth and metastasis.

Genetics

The SERPINE1 gene encoding PAI-1 is located on chromosome 7 (7q21.3-q22). Several polymorphisms in this gene have been associated with variations in PAI-1 levels and activity.

Pharmacology

Several drugs have been developed to inhibit PAI-1, with the aim of preventing or treating thrombosis and other conditions associated with elevated PAI-1 levels. These include anisoylated plasminogen-streptokinase activator complex (APSAC), tissue-type plasminogen activator (tPA), and urokinase-type plasminogen activator (uPA).

See also

• Fibrinolysis
• Thrombosis
• Serpin