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 PLANH1gene 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 serine proteases tPA and uPA/urokinase, and hence is an inhibitor of fibrinolysis, the physiological process that degrades blood clots.
Role in disease
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 inceases synthesis of plasminogen activator inhibitor-1, so it accelerates the development of atherosclerosis.
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