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Plasminogen activator inhibitor-1

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Title: Plasminogen activator inhibitor-1  
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Language: English
Subject: Antithrombin, Coagulation, Fibrinolysis, Vitronectin, Alpha 1-antichymotrypsin
Collection: Fibrinolytic System, Serine Protease Inhibitors
Publisher: World Heritage Encyclopedia

Plasminogen activator inhibitor-1

Serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1
PAI-1 in complex with the SMB domain of Vitronectin
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols  ; PAI; PAI-1; PAI1; PLANH1
External IDs ChEMBL: GeneCards:
RNA expression pattern
Species Human Mouse
UniProt n/a
RefSeq (mRNA)
RefSeq (protein)
Location (UCSC)
PubMed search

Plasminogen activator inhibitor-1 (PAI-1) also known as endothelial plasminogen activator inhibitor or serpin E1 is a protein that in humans is encoded by the SERPINE1 gene. Elevated PAI-1 is a risk factor for thrombosis and atherosclerosis[1]

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.


  • Genetics 1
  • Function 2
  • Role in disease 3
  • Pharmacology 4
  • Interactions 5
  • References 6
  • Further reading 7
  • External links 8


The PAI-1 gene is SERPINE1, located on chromosome 7 (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 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.

PAI-1 inhibits the activity of matrix metalloproteinases, which play a crucial role in invasion of malignant cells across the basal lamina.

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 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.[2]


Plasminogen activator inhibitor-1 has been shown to interact with ORM1.[3]


  1. ^ Vaughan DE (Aug 2005). "PAI-1 and atherothrombosis". Journal of Thrombosis and Haemostasis 3 (8): 1879–83.  
  2. ^ Elokdah H, Abou-Gharbia M, Hennan JK, McFarlane G, Mugford CP, Krishnamurthy G, Crandall DL (July 2004). "Tiplaxtinin, a novel, orally efficacious inhibitor of plasminogen activator inhibitor-1: design, synthesis, and preclinical characterization". J. Med. Chem. 47 (14): 3491–4.  
  3. ^ Boncela J, Papiewska I, Fijalkowska I, Walkowiak B, Cierniewski CS (Sep 2001). "Acute phase protein alpha 1-acid glycoprotein interacts with plasminogen activator inhibitor type 1 and stabilizes its inhibitory activity". J. Biol. Chem. 276 (38): 35305–11.  

Further reading

  • Mimuro J (1991). "[Type 1 plasminogen activator inhibitor: its role in biological reactions]". Rinsho Ketsueki 32 (5): 487–9.  
  • Binder BR, Christ G, Gruber F, Grubic N, Hufnagl P, Krebs M, Mihaly J, Prager GW (2002). "Plasminogen activator inhibitor 1: physiological and pathophysiological roles". News Physiol. Sci. 17: 56–61.  
  • Eddy AA (2002). "Plasminogen activator inhibitor-1 and the kidney". Am. J. Physiol. Renal Physiol. 283 (2): F209–20.  
  • Schroeck F, Arroyo de Prada N, Sperl S, Schmitt M, Viktor M (2003). "Interaction of plasminogen activator inhibitor type-1 (PAI-1) with vitronectin (Vn): mapping the binding sites on PAI-1 and Vn". Biol. Chem. 383 (7–8): 1143–9.  
  • Gils A, Declerck PJ (2004). "The structural basis for the pathophysiological relevance of PAI-I in cardiovascular diseases and the development of potential PAI-I inhibitors". Thromb. Haemost. 91 (3): 425–37.  
  • Durand MK, Bødker JS, Christensen A, Dupont DM, Hansen M, Jensen JK, Kjelgaard S, Mathiasen L, Pedersen KE, Skeldal S, Wind T, Andreasen PA (2004). "Plasminogen activator inhibitor-I and tumour growth, invasion, and metastasis". Thromb. Haemost. 91 (3): 438–49.  
  • Harbeck N, Kates RE, Gauger K, Willems A, Kiechle M, Magdolen V, Schmitt M (2004). "Urokinase-type plasminogen activator (uPA) and its inhibitor PAI-I: novel tumor-derived factors with a high prognostic and predictive impact in breast cancer". Thromb. Haemost. 91 (3): 450–6.  
  • Hertig A, Rondeau E (2004). "Plasminogen activator inhibitor type 1: the two faces of the same coin". Curr. Opin. Nephrol. Hypertens. 13 (1): 39–44.  
  • Hoekstra T, Geleijnse JM, Schouten EG, Kluft C (2004). "Plasminogen activator inhibitor-type 1: its plasma determinants and relation with cardiovascular risk". Thromb. Haemost. 91 (5): 861–72.  
  • Lijnen HR (2005). "Pleiotropic functions of plasminogen activator inhibitor-1". J. Thromb. Haemost. 3 (1): 35–45.  
  • De Taeye B, Smith LH, Vaughan DE (2005). "Plasminogen activator inhibitor-1: a common denominator in obesity, diabetes and cardiovascular disease". Current Opinion in Pharmacology 5 (2): 149–54.  
  • Dellas C, Loskutoff DJ (2005). "Historical analysis of PAI-1 from its discovery to its potential role in cell motility and disease". Thromb. Haemost. 93 (4): 631–40.  
  • Könsgen D, Mustea A, Lichtenegger W, Sehouli J (2005). "[Role of PAI-1 in gynaecological malignancies]". Zentralblatt für Gynäkologie 127 (3): 125–31.  
  • Hermans PW, Hazelzet JA (2007). "Plasminogen activator inhibitor type 1 gene polymorphism and sepsis". Clin. Infect. Dis. 41 Suppl 7: S453–8.  
  • Alessi MC, Poggi M, Juhan-Vague I (2007). "Plasminogen activator inhibitor-1, adipose tissue and insulin resistance". Curr. Opin. Lipidol. 18 (3): 240–5.  

External links

  • The MEROPS online database for peptidases and their inhibitors: I04.020
  • Plasminogen Activator Inhibitor 1 at the US National Library of Medicine Medical Subject Headings (MeSH)
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