definition of Wikipedia
|Serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1|
PAI-1 in complex with the SMB domain of Vitronectin PDB 1OC0
|External IDs||ChEMBL: GeneCards:|
|RNA expression pattern|
PAI-1 is a serine protease inhibitor (serpin) that functions as the principal inhibitor of tissue plasminogen activator (tPA) and urokinase (uPA), the activators of plasminogen and hence fibrinolysis (the physiological breakdown of blood clots). It is a serine protease inhibitor (serpin) protein (SERPINE1).
The other PAI, plasminogen activator inhibitor-2 (PAI-2) is secreted by the placenta and only present in significant amounts during pregnancy. In addition, protease nexin acts as an inhibitor of tPA and urokinase. PAI-1, however, is the main inhibitor of the plasminogen activators.
The PAI-1 gene is officially called SERPINE1 and is located on the seventh chromosome (7q21.3-q22). There is a common polymorphism known as 4G/5G in the promoter region. The 5G allele is slightly less transcriptionally active than the 4G.
PAI-1 inhibits the activity of matrix metalloproteinases, which play a crucial role in invasion of malignant cells across the basal lamina.
Congenital deficiency of PAI-1 has been reported; as fibrinolysis is not suppressed adequately, it leads to a hemorrhagic diathesis (a tendency to hemorrhage).
PAI-1 is present in increased levels in various disease states (such as a number of forms of cancer), as well as in obesity and the metabolic syndrome. It has been linked to the increased occurrence of thrombosis in patients with these conditions.
In inflammatory conditions in which fibrin is deposited in tissues, PAI-1 appears to play a significant role in the progression to fibrosis (pathological formation of connective tissue). Presumably, lower PAI levels would lead to less suppression of fibrinolysis and conversely a more rapid degradation of the fibrin.
Angiotensin II increases synthesis of plasminogen activator inhibitor-1, so it accelerates the development of atherosclerosis.
Tiplaxtinin (PAI-039) is a small molecule inhibitor that is being studied for use in the attenuation of remodeling of blood vessels, a result of arterial hypertension and activation of the renin-angiotensin system.
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