Plasminogen activator inhibitor-1

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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
Identifiers
Symbol(s)	SERPINE1; PAI; PAI-1; PAI1; PLANH1
External IDs	OMIM: 173360 MGI: 97608 Homologene: 68070
Gene ontology Molecular Function: • protease binding • serine-type endopeptidase inhibitor activity • protein binding • plasminogen activator activity Cellular Component: • extracellular region Biological Process: • blood coagulation • fibrinolysis • regulation of angiogenesis
RNA expression pattern
More reference expression data
Orthologs
	Human	Mouse
Entrez	5054	18787
Ensembl	ENSG00000106366	ENSMUSG00000037411
Uniprot	P05121	Q7TPE9
Refseq	NM_000602 (mRNA) NP_000593 (protein)	NM_008871 (mRNA) NP_032897 (protein)
Location	Chr 7: 100.56 - 100.57 Mb	Chr 5: 137.35 - 137.36 Mb
Pubmed search	[1]	[2]

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Plasminogen activator inhibitor-1 is 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.

Genetics

The PLANH1 gene 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.

Function

PAI-1 is mainly produced by the endothelium (cells lining blood vessels), but is also secreted by other tissue types, such as adipose tissue.

PAI-1 inhibits the serine proteases tPA and uPA/urokinase, and hence is an inhibitor of fibrinolysis, the physiological process that degrades blood clots.

Fibrinolysis (simplified). Blue arrows denote stimulation, and red arrows inhibition.

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.

Pharmacology

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.^[1]

References

Further reading

External links

• MeSH Plasminogen+Activator+Inhibitor+1

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