Tissue plasminogen activator

Tissue plasminogen activator

Tissue plasminogen activator (abbreviated tPA or PLAT) is a protein involved in the breakdown of blood clots. Specifically, it is a serine protease (EC number| found on endothelial cells, the cells that line the blood vessels. As an enzyme, it catalyzes the conversion of plasminogen to plasmin, the major enzyme responsible for clot breakdown. Because it works on the clotting system, tPA is used in clinical medicine to treat stroke.


The classic role of tPA is in the clotting system. Specifically, tPA catalyzes the conversion of plasminogen into plasmin. It does so by cleaving the single-chained plasminogen into two chains. These two chains are linked by a disulfide bond and the resulting molecule is called plasmin.

Increased enzymatic activity causes hyperfibrinolysis, which manifests as excessive bleeding. Decreased activity leads to hypofibrinolysis which can result in thrombosis or embolism.

Tissue plasminogen activator also plays a role in cell migration and tissue remodeling.


Tissue plasminogen activator is a protein encoded by the "PLAT" gene, which is located on chromosome 8. The primary transcript produced by this gene undergoes alternative splicing, producing three distinct messenger RNAs.

Clinical applications

Recombinant tPA is used in diseases that feature blood clots, such as pulmonary embolism, myocardial infarction and stroke. To be effective, tPA must be administered within the first three hours of the event to be given intravenously, or within six hours to be administered through an arterial catheter directly to the site of occlusion. The guideline in Ontario, Canada hospitals for ischemic strokes is that tPA must be given within 3 hours of the onset of symptoms. Because of this, only about 3% of patients qualify for this treatment. tPA appears to show benefit not only for large artery occlusions but also for lacunar strokes. Since tPA dissolves blood clots, there is risk of hemorrhage with its use.

Recently tPA has been used to dissolve thrombi associated with ischemic strokes and brain injury.

In addition, people with frostbite that were treated with tPA had fewer amputations than those that were not.cite journal | author = Bruen KJ, Ballard JR, Morris SE, Cochran A, Edelman LS, Saffle JR | title = Reduction of the incidence of amputation in frostbite injury with thrombolytic therapy | journal = Arch Surg | volume = 142 | issue = 6 | pages = 546–51; discussion 551–3 | year = 2007 | month = June | pmid = 17576891 | doi = 10.1001/archsurg.142.6.546 | url = | issn = ]

ee also

* Thrombolysis
* Ultrasound-Enhanced Systemic Thrombolysis


Further reading

citations =
*cite journal | author=Rijken DC |title=Relationships between structure and function of tissue-type plasminogen activator |journal=Klin. Wochenschr. |volume=66 Suppl 12 |issue= |pages= 33–9 |year= 1988 |pmid= 3126346 |doi=
*cite journal | author=Bode W, Renatus M |title=Tissue-type plasminogen activator: variants and crystal/solution structures demarcate structural determinants of function |journal=Curr. Opin. Struct. Biol. |volume=7 |issue= 6 |pages= 865–72 |year= 1998 |pmid= 9434908 |doi=
* Collen D, Billiau A, Edy J, De Somer P., Identification of the human plasma protein which inhibits fibrinolysis associated with malignant cells, Biochim Biophys Acta. 1977 Sep 29;499(2):194-201
*cite journal | author=Anglés-Cano E, Rojas G |title=Apolipoprotein(a): structure-function relationship at the lysine-binding site and plasminogen activator cleavage site |journal=Biol. Chem. |volume=383 |issue= 1 |pages= 93–9 |year= 2003 |pmid= 11928826 |doi=
*cite journal | author=Ny T, Wahlberg P, Brändström IJ |title=Matrix remodeling in the ovary: regulation and functional role of the plasminogen activator and matrix metalloproteinase systems |journal=Mol. Cell. Endocrinol. |volume=187 |issue= 1-2 |pages= 29–38 |year= 2003 |pmid= 11988309 |doi=
*cite journal | author=Teesalu T, Kulla A, Asser T, "et al." |title=Tissue plasminogen activator as a key effector in neurobiology and neuropathology |journal=Biochem. Soc. Trans. |volume=30 |issue= 2 |pages= 183–9 |year= 2002 |pmid= 12023848 |doi= 10.1042/ |doi_brokendate=2008-06-21
*cite journal | author=Pang PT, Lu B |title=Regulation of late-phase LTP and long-term memory in normal and aging hippocampus: role of secreted proteins tPA and BDNF |journal=Ageing Res. Rev. |volume=3 |issue= 4 |pages= 407–30 |year= 2005 |pmid= 15541709 |doi= 10.1016/j.arr.2004.07.002
*cite journal | author=Sheehan JJ, Tsirka SE |title=Fibrin-modifying serine proteases thrombin, tPA, and plasmin in ischemic stroke: a review |journal=Glia |volume=50 |issue= 4 |pages= 340–50 |year= 2005 |pmid= 15846799 |doi= 10.1002/glia.20150

External links

* http://www.americanheart.org/presenter.jhtml?identifier=4751
* [http://www.sciam.com/article.cfm?chanID=sa004&articleID=00055D80-04DC-12D8-BDFD83414B7F0000 Widening the Window : Strategies to buy time in treating ischemic stroke] - Scientific American Magazine (August 2005)

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Look at other dictionaries:

  • tissue plasminogen activator — n a clot dissolving enzyme that has an affinity for fibrin, that catalyzes the conversion of plasminogen to plasmin, that is produced naturally in blood vessel linings, and that is used in a genetically engineered form to prevent damage to heart… …   Medical dictionary

  • tissue plasminogen activator — n. an enzyme produced by the blood vessels that dissolves blood clots by converting plasminogen into plasmin: it is manufactured using recombinant DNA technology and used to prevent stroke, etc …   English World dictionary

  • tissue plasminogen activator — noun a thrombolytic agent (trade name Activase) that causes fibrinolysis at the site of a blood clot; used in treating acute myocardial infarction • Syn: ↑Activase • Usage Domain: ↑trade name (for: ↑Activase) • Hypernyms: ↑ …   Useful english dictionary

  • tissue plasminogen activator — An enzyme made in the body that helps dissolve blood clots. A form of this enzyme is made in the laboratory to treat heart attacks, strokes, and clots in the lungs. It is also being studied in the treatment of cancer. Tissue plasminogen activator …   English dictionary of cancer terms

  • tissue plasminogen activator — (= TPA; tPA) Plasma serine protease, one of a closely related group of plasminogen activators. Contains an EGF like domain and multiple copies of the kringle domain …   Dictionary of molecular biology

  • recombinant tissue plasminogen activator — A form of tissue plasminogen activator that is made in the laboratory. It helps dissolve blood clots and is used to treat heart attacks, strokes, and clots in the lungs. It is also being studied in the treatment of cancer. It is a type of… …   English dictionary of cancer terms

  • tissue plasminogen activator — noun Date: 1981 a clot dissolving enzyme with an affinity for fibrin that is produced naturally in blood vessel linings and is used in a genetically engineered form to prevent damage to heart muscle following a heart attack and reduce… …   New Collegiate Dictionary

  • Tissue plasminogen activator — Activateur tissulaire du plasminogène Fibrinolyse. L activateur tissulaire du plasminogène (t PA) est une enzyme protéolytique initiant la fibrinolyse. Elle est sécrété par l endothélium vasculaire plusieurs jours après lésion de celui ci et son… …   Wikipédia en Français

  • tissue plasminogen activator — Biochem. 1. an anticlotting enzyme, naturally occurring in small amounts in the blood. 2. Pharm. the same enzyme, produced in large amounts by genetic engineering techniques for use in dissolving blood clots. Abbr.: TPA * * * …   Universalium

  • Tissue Plasminogen Activator — Tis|sue Plas|mi|no|gen Ac|ti|va|tor [ tɪʃju plæsmɪnədʒən aektɪ veɪtə[r]; engl. = Gewebeplasminogenaktivator]: svw. ↑ tPA …   Universal-Lexikon

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