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|3.4.21.68) 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.
Function
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.
Genetics
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
References
Further reading
PBB_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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