Plasminogen activator inhibitor-1: Difference between revisions

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Latest revision as of 20:40, 23 February 2018

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

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.

Function

PAI-1's main function entails the inhibition of urokinase plasminogen activator (uPA), an enzyme responsible for the cleavage of plasminogen to form plasmin. Plasmin mediates the degradation of the extracellular matrix either by itself or in conjunction with matrix metalloproteinases. In this scenario, PAI-1 inhibits uPA via active site binding, preventing the formation of plasmin. Additional inhibition is mediated by PAI-1 binding to the uPA/uPA receptor complex, resulting in the latter's degradation.^[2] Thus, PAI can be said to inhibit the serine proteases tPA and uPA/urokinase, and hence is an inhibitor of fibrinolysis, the physiological process that degrades blood clots. In addition, PAI-1 inhibits the activity of matrix metalloproteinases, which play a crucial role in invasion of malignant cells through the basal lamina.

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

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.

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.^[3]
Annonacinone is a naturally occurring PAI-1 inhibitor found in plants of the Annonaceae family.^[4]

Interactions

Plasminogen activator inhibitor-1 has been shown to interact with ORM1.^[5]

References

↑ Vaughan DE (August 2005). "PAI-1 and atherothrombosis". Journal of Thrombosis and Haemostasis. 3 (8): 1879–83. doi:10.1111/j.1538-7836.2005.01420.x. PMID 16102055.
↑ Carter JC, Church FC (2009). "Obesity and breast cancer: the roles of peroxisome proliferator-activated receptor-γ and plasminogen activator inhibitor-1". PPAR Research. 2009: 345320. doi:10.1155/2009/345320. PMC 2723729. PMID 19672469.
↑ 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". Journal of Medicinal Chemistry. 47 (14): 3491–4. doi:10.1021/jm049766q. PMID 15214776.
↑ Pautus S, Alami M, Adam F, Bernadat G, Lawrence DA, De Carvalho A, Ferry G, Rupin A, Hamze A, Champy P, Bonneau N, Gloanec P, Peglion JL, Brion JD, Bianchini EP, Borgel D (2016). "Characterization of the Annonaceous acetogenin, annonacinone, a natural product inhibitor of plasminogen activator inhibitor-1". Scientific Reports. 6: 36462. doi:10.1038/srep36462. PMC 5120274. PMID 27876785.
↑ Boncela J, Papiewska I, Fijalkowska I, Walkowiak B, Cierniewski CS (September 2001). "Acute phase protein alpha 1-acid glycoprotein interacts with plasminogen activator inhibitor type 1 and stabilizes its inhibitory activity". The Journal of Biological Chemistry. 276 (38): 35305–11. doi:10.1074/jbc.M104028200. PMID 11418606.

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)

[pmid16102055-1] Vaughan DE (August 2005). "PAI-1 and atherothrombosis". Journal of Thrombosis and Haemostasis. 3 (8): 1879–83. doi:10.1111/j.1538-7836.2005.01420.x. PMID 16102055.

[2] Carter JC, Church FC (2009). "Obesity and breast cancer: the roles of peroxisome proliferator-activated receptor-γ and plasminogen activator inhibitor-1". PPAR Research. 2009: 345320. doi:10.1155/2009/345320. PMC 2723729. PMID 19672469.

[3] 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". Journal of Medicinal Chemistry. 47 (14): 3491–4. doi:10.1021/jm049766q. PMID 15214776.

[Pautus_2016-4] Pautus S, Alami M, Adam F, Bernadat G, Lawrence DA, De Carvalho A, Ferry G, Rupin A, Hamze A, Champy P, Bonneau N, Gloanec P, Peglion JL, Brion JD, Bianchini EP, Borgel D (2016). "Characterization of the Annonaceous acetogenin, annonacinone, a natural product inhibitor of plasminogen activator inhibitor-1". Scientific Reports. 6: 36462. doi:10.1038/srep36462. PMC 5120274. PMID 27876785.

[pmid11418606-5] Boncela J, Papiewska I, Fijalkowska I, Walkowiak B, Cierniewski CS (September 2001). "Acute phase protein alpha 1-acid glycoprotein interacts with plasminogen activator inhibitor type 1 and stabilizes its inhibitory activity". The Journal of Biological Chemistry. 276 (38): 35305–11. doi:10.1074/jbc.M104028200. PMID 11418606.

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@@ Line 1: / Line 1: @@
-{{PBB_Controls
+{{Infobox_gene}}
-| update_page = yes
-| require_manual_inspection = no
-| update_protein_box = yes
-| update_summary = no
-| update_citations = yes
-}}
-{{GNF_Protein_box
- | image = 1OC0.png
- | image_source = PAI-1 in complex with the SMB domain of [[Vitronectin]] {{PDB|1OC0}}
- | Name = Serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1
- | HGNCid = 8583
- | Symbol = SERPINE1
- | AltSymbols =; PAI; PAI-1; PAI1; PLANH1
- | OMIM = 173360
- | ECnumber =
- | Homologene = 68070
- | MGIid = 97608
- | GeneAtlas_image1 = PBB_GE_SERPINE1_202627_s_at_tn.png
- | GeneAtlas_image2 = PBB_GE_SERPINE1_202628_s_at_tn.png
- <!-- The Following entry is a time stamp of the last bot update.  It is typically hidden data -->
- | DateOfBotUpdate = 07:36, 9 October 2007 (UTC)
- | Function = {{GNF_GO|id=GO:0002020 |text = protease binding}} {{GNF_GO|id=GO:0004867 |text = serine-type endopeptidase inhibitor activity}} {{GNF_GO|id=GO:0005515 |text = protein binding}} {{GNF_GO|id=GO:0008243 |text = plasminogen activator activity}}
- | Component = {{GNF_GO|id=GO:0005576 |text = extracellular region}}
- | Process = {{GNF_GO|id=GO:0007596 |text = blood coagulation}} {{GNF_GO|id=GO:0042730 |text = fibrinolysis}} {{GNF_GO|id=GO:0045765 |text = regulation of angiogenesis}}
- | Orthologs = {{GNF_Ortholog_box
-    | Hs_EntrezGene = 5054
-    | Hs_Ensembl = ENSG00000106366
-    | Hs_RefseqProtein = NP_000593
-    | Hs_RefseqmRNA = NM_000602
-    | Hs_GenLoc_db =
-    | Hs_GenLoc_chr = 7
-    | Hs_GenLoc_start = 100557172
-    | Hs_GenLoc_end = 100569026
-    | Hs_Uniprot = P05121
-    | Mm_EntrezGene = 18787
-    | Mm_Ensembl = ENSMUSG00000037411
-    | Mm_RefseqmRNA = NM_008871
-    | Mm_RefseqProtein = NP_032897
-    | Mm_GenLoc_db =
-    | Mm_GenLoc_chr = 5
-    | Mm_GenLoc_start = 137346135
-    | Mm_GenLoc_end = 137356886
-    | Mm_Uniprot = Q7TPE9
-  }}
-}}
-{{SI}}
-{{CMG}}
-{{EH}}
+'''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]]<ref name="pmid16102055">{{cite journal | vauthors = Vaughan DE | title = PAI-1 and atherothrombosis | journal = Journal of Thrombosis and Haemostasis | volume = 3 | issue = 8 | pages = 1879–83 | date = August 2005 | pmid = 16102055 | doi = 10.1111/j.1538-7836.2005.01420.x }}</ref>
-'''Plasminogen activator inhibitor-1''' is the principal inhibitor of [[tissue plasminogen activator]] (tPA) and [[urokinase]] (uPA), the activators of [[plasmin]]ogen and hence [[fibrinolysis]] (the physiological breakdown of [[thrombus|blood clots]]). It is a [[serine protease inhibitor]] (serpin) protein (SERPINE1).
+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 [[plasmin]]ogen and hence [[fibrinolysis]] (the physiological breakdown of [[thrombus|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 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 (biology)|polymorphism]] known as 4G/5G in the promoter region. The 5G allele is slightly less transcriptionally active than the 4G.
+The PAI-1 [[gene]] is ''SERPINE1'', located on [[chromosome 7]] (7q21.3-q22). There is a common [[Polymorphism (biology)|polymorphism]] known as 4G/5G in the promoter region. The 5G allele is slightly less transcriptionally active than the 4G.
+== Function ==
+PAI-1's main function entails the inhibition of [[urokinase plasminogen activator]] (uPA), an enzyme responsible for the cleavage of [[plasminogen]] to form [[plasmin]]. Plasmin mediates the degradation of the extracellular matrix either by itself or in conjunction with matrix metalloproteinases. In this scenario, PAI-1 inhibits uPA via active site binding, preventing the formation of plasmin. Additional inhibition is mediated by PAI-1 binding to the uPA/uPA receptor complex, resulting in the latter's degradation.<ref>{{cite journal | vauthors = Carter JC, Church FC | title = Obesity and breast cancer: the roles of peroxisome proliferator-activated receptor-γ and plasminogen activator inhibitor-1 | journal = PPAR Research | volume = 2009 | pages = 345320 | date = 2009 | pmid = 19672469 | doi = 10.1155/2009/345320 | pmc=2723729}}</ref> Thus, PAI can be said to inhibit the [[serine protease]]s tPA and uPA/urokinase, and hence is an inhibitor of [[fibrinolysis]], the physiological process that degrades blood clots. In addition, PAI-1 inhibits the activity of matrix metalloproteinases, which play a crucial role in invasion of malignant cells through the [[basal lamina]].
-==Function==
 PAI-1 is mainly produced by the [[endothelium]] (cells lining [[blood vessel]]s), but is also secreted by other tissue types, such as [[adipose tissue]].
-PAI-1 inhibits the [[serine protease]]s tPA and uPA/urokinase, and hence is an inhibitor of [[fibrinolysis]], the physiological process that degrades blood clots.
 [[Image:Fibrinolysis.png|center|framed|Fibrinolysis (simplified). Blue arrows denote stimulation, and red arrows inhibition.]]
@@ Line 71: / Line 25: @@
 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.
+Angiotensin II increases 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]].<ref>Elokdah H, Abou-Gharbia M, Hennan JK, McFarlane G, Mugford CP, Krishnamurthy G, Crandall DL. Tiplaxtinin, a novel, orally efficacious inhibitor of plasminogen activator inhibitor-1: design, synthesis, and preclinical characterization. ''J Med Chem'' 2004;47:3491-4. PMID 15214776.</ref>
+* [[Tiplaxtinin]] (PAI-039) is a small molecule inhibitor that is being studied for use in the attenuation of [[arterial remodeling|remodeling]] of blood vessels, a result of [[arterial hypertension]] and activation of the [[renin–angiotensin system]].<ref>{{cite journal | vauthors = Elokdah H, Abou-Gharbia M, Hennan JK, McFarlane G, Mugford CP, Krishnamurthy G, Crandall DL | title = Tiplaxtinin, a novel, orally efficacious inhibitor of plasminogen activator inhibitor-1: design, synthesis, and preclinical characterization | journal = Journal of Medicinal Chemistry | volume = 47 | issue = 14 | pages = 3491–4 | date = July 2004 | pmid = 15214776 | doi = 10.1021/jm049766q }}</ref>
+* [[Annonacinone]] is a naturally occurring PAI-1 inhibitor found in plants of the ''[[Annonaceae]]'' family.<ref name="Pautus_2016">{{cite journal | vauthors = Pautus S, Alami M, Adam F, Bernadat G, Lawrence DA, De Carvalho A, Ferry G, Rupin A, Hamze A, Champy P, Bonneau N, Gloanec P, Peglion JL, Brion JD, Bianchini EP, Borgel D | title = Characterization of the Annonaceous acetogenin, annonacinone, a natural product inhibitor of plasminogen activator inhibitor-1 | journal = Scientific Reports | volume = 6 | issue = | pages = 36462 | year = 2016 | pmid = 27876785 | pmc = 5120274 | doi = 10.1038/srep36462 }}</ref>
-==References==
+== Interactions ==
+Plasminogen activator inhibitor-1 has been shown to [[Protein-protein interaction|interact]] with [[ORM1]].<ref name=pmid11418606>{{cite journal | vauthors = Boncela J, Papiewska I, Fijalkowska I, Walkowiak B, Cierniewski CS | title = Acute phase protein alpha 1-acid glycoprotein interacts with plasminogen activator inhibitor type 1 and stabilizes its inhibitory activity | journal = The Journal of Biological Chemistry | volume = 276 | issue = 38 | pages = 35305–11 | date = September 2001 | pmid = 11418606 | doi = 10.1074/jbc.M104028200 }}</ref>
+== References ==
 {{reflist}}
-==Further reading==
+== Further reading ==
 {{refbegin | 2}}
-{{PBB_Further_reading
+* {{cite journal | vauthors = Mimuro J | title = [Type 1 plasminogen activator inhibitor: its role in biological reactions] | journal = [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology | volume = 32 | issue = 5 | pages = 487–9 | date = May 1991 | pmid = 1870265 | doi =  }}
-| citations =
+* {{cite journal | vauthors = Binder BR, Christ G, Gruber F, Grubic N, Hufnagl P, Krebs M, Mihaly J, Prager GW | title = Plasminogen activator inhibitor 1: physiological and pathophysiological roles | journal = News in Physiological Sciences | volume = 17 | issue =  | pages = 56–61 | date = April 2002 | pmid = 11909993 | doi =  }}
-*{{cite journal  | author=Mimuro J |title=[Type 1 plasminogen activator inhibitor: its role in biological reactions] |journal=Rinsho Ketsueki |volume=32 |issue= 5 |pages= 487-9 |year= 1991 |pmid= 1870265 |doi=  }}
+* {{cite journal | vauthors = Eddy AA | title = Plasminogen activator inhibitor-1 and the kidney | journal = American Journal of Physiology. Renal Physiology | volume = 283 | issue = 2 | pages = F209-20 | date = August 2002 | pmid = 12110504 | doi = 10.1152/ajprenal.00032.2002 }}
-*{{cite journal  | author=Binder BR, Christ G, Gruber F, ''et al.'' |title=Plasminogen activator inhibitor 1: physiological and pathophysiological roles. |journal=News Physiol. Sci. |volume=17 |issue=  |pages= 56-61 |year= 2002 |pmid= 11909993 |doi=  }}
+* {{cite journal |vauthors=Wang J, Li J, Liu Q | title = Association between platelet activation and fibrinolysis in acute stroke patients | journal = Neurosci. Lett. | volume = 384 | issue = 3 | pages = 305–9 |date=August 2005 | pmid = 15916851 | doi =10.1016/j.neulet.2005.04.090}}
-*{{cite journal  | author=Eddy AA |title=Plasminogen activator inhibitor-1 and the kidney. |journal=Am. J. Physiol. Renal Physiol. |volume=283 |issue= 2 |pages= F209-20 |year= 2002 |pmid= 12110504 |doi= 10.1152/ajprenal.00032.2002 }}
+* {{cite journal | vauthors = Schroeck F, Arroyo de Prada N, Sperl S, Schmitt M, Viktor M | title = Interaction of plasminogen activator inhibitor type-1 (PAI-1) with vitronectin (Vn): mapping the binding sites on PAI-1 and Vn | journal = Biological Chemistry | volume = 383 | issue = 7-8 | pages = 1143–9 | year = 2003 | pmid = 12437099 | doi = 10.1515/BC.2002.125 }}
-*{{cite journal  | author=Schroeck F, Arroyo de Prada N, Sperl S, ''et al.'' |title=Interaction of plasminogen activator inhibitor type-1 (PAI-1) with vitronectin (Vn): mapping the binding sites on PAI-1 and Vn. |journal=Biol. Chem. |volume=383 |issue= 7-8 |pages= 1143-9 |year= 2003 |pmid= 12437099 |doi=  }}
+* {{cite journal | vauthors = Gils A, Declerck PJ | title = The structural basis for the pathophysiological relevance of PAI-I in cardiovascular diseases and the development of potential PAI-I inhibitors | journal = Thrombosis and Haemostasis | volume = 91 | issue = 3 | pages = 425–37 | date = March 2004 | pmid = 14983217 | doi = 10.1160/TH03-12-0764 }}
-*{{cite journal  | author=Gils A, Declerck PJ |title=The structural basis for the pathophysiological relevance of PAI-I in cardiovascular diseases and the development of potential PAI-I inhibitors. |journal=Thromb. Haemost. |volume=91 |issue= 3 |pages= 425-37 |year= 2004 |pmid= 14983217 |doi= 10.1160/TH03-12-0764 }}
+* {{cite journal | vauthors = Durand MK, Bødker JS, Christensen A, Dupont DM, Hansen M, Jensen JK, Kjelgaard S, Mathiasen L, Pedersen KE, Skeldal S, Wind T, Andreasen PA | title = Plasminogen activator inhibitor-I and tumour growth, invasion, and metastasis | journal = Thrombosis and Haemostasis | volume = 91 | issue = 3 | pages = 438–49 | date = March 2004 | pmid = 14983218 | doi = 10.1160/TH03-12-0784 }}
-*{{cite journal  | author=Durand MK, Bødker JS, Christensen A, ''et al.'' |title=Plasminogen activator inhibitor-I and tumour growth, invasion, and metastasis. |journal=Thromb. Haemost. |volume=91 |issue= 3 |pages= 438-49 |year= 2004 |pmid= 14983218 |doi= 10.1160/TH03-12-0784 }}
+* {{cite journal | vauthors = Harbeck N, Kates RE, Gauger K, Willems A, Kiechle M, Magdolen V, Schmitt M | title = Urokinase-type plasminogen activator (uPA) and its inhibitor PAI-I: novel tumor-derived factors with a high prognostic and predictive impact in breast cancer | journal = Thrombosis and Haemostasis | volume = 91 | issue = 3 | pages = 450–6 | date = March 2004 | pmid = 14983219 | doi = 10.1160/TH03-12-0798 }}
-*{{cite journal  | author=Harbeck N, Kates RE, Gauger K, ''et al.'' |title=Urokinase-type plasminogen activator (uPA) and its inhibitor PAI-I: novel tumor-derived factors with a high prognostic and predictive impact in breast cancer. |journal=Thromb. Haemost. |volume=91 |issue= 3 |pages= 450-6 |year= 2004 |pmid= 14983219 |doi= 10.1160/TH03-12-0798 }}
+* {{cite journal | vauthors = Hertig A, Rondeau E | title = Plasminogen activator inhibitor type 1: the two faces of the same coin | journal = Current Opinion in Nephrology and Hypertension | volume = 13 | issue = 1 | pages = 39–44 | date = January 2004 | pmid = 15090858 | doi = 10.1097/00041552-200401000-00006 }}
-*{{cite journal  | author=Hertig A, Rondeau E |title=Plasminogen activator inhibitor type 1: the two faces of the same coin. |journal=Curr. Opin. Nephrol. Hypertens. |volume=13 |issue= 1 |pages= 39-44 |year= 2004 |pmid= 15090858 |doi=  }}
+* {{cite journal | vauthors = Hoekstra T, Geleijnse JM, Schouten EG, Kluft C | title = Plasminogen activator inhibitor-type 1: its plasma determinants and relation with cardiovascular risk | journal = Thrombosis and Haemostasis | volume = 91 | issue = 5 | pages = 861–72 | date = May 2004 | pmid = 15116245 | doi = 10.1160/TH03-08-0546 }}
-*{{cite journal  | author=Hoekstra T, Geleijnse JM, Schouten EG, Kluft C |title=Plasminogen activator inhibitor-type 1: its plasma determinants and relation with cardiovascular risk. |journal=Thromb. Haemost. |volume=91 |issue= 5 |pages= 861-72 |year= 2004 |pmid= 15116245 |doi= 10.1267/THRO04050861 }}
+* {{cite journal | vauthors = Lijnen HR | title = Pleiotropic functions of plasminogen activator inhibitor-1 | journal = Journal of Thrombosis and Haemostasis | volume = 3 | issue = 1 | pages = 35–45 | date = January 2005 | pmid = 15634264 | doi = 10.1111/j.1538-7836.2004.00827.x }}
-*{{cite journal  | author=Lijnen HR |title=Pleiotropic functions of plasminogen activator inhibitor-1. |journal=J. Thromb. Haemost. |volume=3 |issue= 1 |pages= 35-45 |year= 2005 |pmid= 15634264 |doi= 10.1111/j.1538-7836.2004.00827.x }}
+* {{cite journal | vauthors = De Taeye B, Smith LH, Vaughan DE | title = Plasminogen activator inhibitor-1: a common denominator in obesity, diabetes and cardiovascular disease | journal = Current Opinion in Pharmacology | volume = 5 | issue = 2 | pages = 149–54 | date = April 2005 | pmid = 15780823 | doi = 10.1016/j.coph.2005.01.007 }}
-*{{cite journal  | author=De Taeye B, Smith LH, Vaughan DE |title=Plasminogen activator inhibitor-1: a common denominator in obesity, diabetes and cardiovascular disease. |journal=Current opinion in pharmacology |volume=5 |issue= 2 |pages= 149-54 |year= 2005 |pmid= 15780823 |doi= 10.1016/j.coph.2005.01.007 }}
+* {{cite journal | vauthors = Dellas C, Loskutoff DJ | title = Historical analysis of PAI-1 from its discovery to its potential role in cell motility and disease | journal = Thrombosis and Haemostasis | volume = 93 | issue = 4 | pages = 631–40 | date = April 2005 | pmid = 15841306 | doi = 10.1160/TH05-01-0033}}
-*{{cite journal  | author=Dellas C, Loskutoff DJ |title=Historical analysis of PAI-1 from its discovery to its potential role in cell motility and disease. |journal=Thromb. Haemost. |volume=93 |issue= 4 |pages= 631-40 |year= 2005 |pmid= 15841306 |doi= 10.1267/THRO05040631 }}
+* {{cite journal | vauthors = Könsgen D, Mustea A, Lichtenegger W, Sehouli J | title = [Role of PAI-1 in gynaecological malignancies] | journal = Zentralblatt für Gynäkologie | volume = 127 | issue = 3 | pages = 125–31 | date = June 2005 | pmid = 15915389 | doi = 10.1055/s-2005-836407 }}
-*{{cite journal  | author=Könsgen D, Mustea A, Lichtenegger W, Sehouli J |title=[Role of PAI-1 in gynaecological malignancies] |journal=Zentralblatt für Gynäkologie |volume=127 |issue= 3 |pages= 125-31 |year= 2005 |pmid= 15915389 |doi= 10.1055/s-2005-836407 }}
+* {{cite journal | vauthors = Hermans PW, Hazelzet JA | title = Plasminogen activator inhibitor type 1 gene polymorphism and sepsis | journal = Clinical Infectious Diseases | volume = 41 Suppl 7 | issue =  | pages = S453-8 | date = November 2005 | pmid = 16237647 | doi = 10.1086/431996 }}
-*{{cite journal  | author=Vaughan DE |title=PAI-1 and atherothrombosis. |journal=J. Thromb. Haemost. |volume=3 |issue= 8 |pages= 1879-83 |year= 2005 |pmid= 16102055 |doi= 10.1111/j.1538-7836.2005.01420.x }}
+* {{cite journal | vauthors = Alessi MC, Poggi M, Juhan-Vague I | title = Plasminogen activator inhibitor-1, adipose tissue and insulin resistance | journal = Current Opinion in Lipidology | volume = 18 | issue = 3 | pages = 240–5 | date = June 2007 | pmid = 17495595 | doi = 10.1097/MOL.0b013e32814e6d29 }}
-*{{cite journal  | author=Hermans PW, Hazelzet JA |title=Plasminogen activator inhibitor type 1 gene polymorphism and sepsis. |journal=Clin. Infect. Dis. |volume=41 Suppl 7 |issue=  |pages= S453-8 |year= 2007 |pmid= 16237647 |doi= 10.1086/431996 }}
-*{{cite journal  | author=Alessi MC, Poggi M, Juhan-Vague I |title=Plasminogen activator inhibitor-1, adipose tissue and insulin resistance. |journal=Curr. Opin. Lipidol. |volume=18 |issue= 3 |pages= 240-5 |year= 2007 |pmid= 17495595 |doi= 10.1097/MOL.0b013e32814e6d29 }}
-}}
 {{refend}}
-==External links==
+== External links ==
+* The [[MEROPS]] online database for peptidases and their inhibitors: [http://merops.sanger.ac.uk/cgi-bin/merops.cgi?id=I04.020 I04.020]
 * {{MeshName|Plasminogen+Activator+Inhibitor+1}}
+{{PDB Gallery|geneid=5054}}
 {{Coagulation}}
 {{Serpins}}
-{SIB}}
 [[Category:Fibrinolytic system]]
 [[Category:Serine protease inhibitors]]
-[[Category:Hematology]]
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v t e Serpins
inhibitory	Alpha 1-antichymotrypsin Alpha 1-antitrypsin Alpha 2-antiplasmin Antithrombin C1-inhibitor Heparin cofactor II Protein C inhibitor Plasminogen activator inhibitor-1 Plasminogen activator inhibitor-2 Protein Z-related protease inhibitor SERPINA1 SERPINA2 SERPINA3 SERPINA4 SERPINA5 SERPINA9 SERPINA14 SERPINB1 SERPINB2 SERPINB3 SERPINB4 SERPINB5 SERPINB6 SERPINB7 SERPINB8 SERPINB9 SERPINB13 SERPINC1 SERPIND1 SERPINE1 SERPINE2 SERPINE2 SERPINF1 SERPING1 SERPINH1 SERPINI1 SERPINI2
Cross class inhibitory	MENT SCCA-1 CrmA
noninhibitory	Heat shock protein 47 Maspin Ovalbumin SERPINF1 Transcortin Thyroxine-binding globulin Angiotensinogen SERPINF1
see also disorders of globin and globulin proteins