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Tissue plasminogen activator

 

 
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Tissue plasminogen activator
 
 
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Tissue plasminogen activator (abbreviated tPA or PLAT) is a protein
Protein

Proteins are organic compounds made of amino acids arranged in a linear chain and joined together by peptide bonds between the carboxyl and amino groups of adjacent amino acid Residue ....
 involved in the breakdown of blood clots. Specifically, it is a serine protease
Serine protease

Serine proteases or serine endopeptidases are proteases in which one of the amino acids at the active site is serine.They are found in both single-cell and complex organisms, in both cells with nuclei and without nuclei ....
  found on endothelial cells, the cells that line the blood vessel
Blood vessel

The blood vessels are the part of the circulatory system that transport blood throughout the body. There are three major types of blood vessels: the artery, which carry the blood away from the heart, the capillary, which enable the actual exchange of water and chemicals between the blood and the tissues; and the veins, which carry blood from...
s. As an enzyme
Enzyme

Enzymes are biomolecules that catalysis chemical reactions. Almost all enzymes are proteins. In enzymatic reactions, the molecules at the beginning of the process are called Substrate , and the enzyme converts them into different molecules, the products....
, it catalyzes
Catalysis

Catalysis is the process in which the reaction rate of a chemical reaction is either increased or decreased by means of a chemical substance known as a catalyst....
 the conversion of plasminogen to plasmin
Plasmin

Plasmin is an important enzyme present in blood that degrades many blood plasma proteins, most notable, fibrin thrombuss. The degradation of fibrin is termed fibrinolysis....
, the major enzyme responsible for clot breakdown. Because it works on the clotting system, tPA is used in clinical medicine
Clinical Medicine

Clinical Medicine, subtitled Journal of the Royal College of Physicians, is a medical journal published bimonthly by the Royal College of Physicians in London....
 to treat stroke
Stroke

A stroke is the rapidly developing loss of brain function due to a disturbance in the blood supply to the brain. According to the National Stroke Association, a "stroke" occurs when a blood clot blocks and artery or a blood vessel breaks, interrupting blood flow to an area of the brain....
.

classic role of tPA is in the clotting system.






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Encyclopedia


Tissue plasminogen activator (abbreviated tPA or PLAT) is a protein
Protein

Proteins are organic compounds made of amino acids arranged in a linear chain and joined together by peptide bonds between the carboxyl and amino groups of adjacent amino acid Residue ....
 involved in the breakdown of blood clots. Specifically, it is a serine protease
Serine protease

Serine proteases or serine endopeptidases are proteases in which one of the amino acids at the active site is serine.They are found in both single-cell and complex organisms, in both cells with nuclei and without nuclei ....
  found on endothelial cells, the cells that line the blood vessel
Blood vessel

The blood vessels are the part of the circulatory system that transport blood throughout the body. There are three major types of blood vessels: the artery, which carry the blood away from the heart, the capillary, which enable the actual exchange of water and chemicals between the blood and the tissues; and the veins, which carry blood from...
s. As an enzyme
Enzyme

Enzymes are biomolecules that catalysis chemical reactions. Almost all enzymes are proteins. In enzymatic reactions, the molecules at the beginning of the process are called Substrate , and the enzyme converts them into different molecules, the products....
, it catalyzes
Catalysis

Catalysis is the process in which the reaction rate of a chemical reaction is either increased or decreased by means of a chemical substance known as a catalyst....
 the conversion of plasminogen to plasmin
Plasmin

Plasmin is an important enzyme present in blood that degrades many blood plasma proteins, most notable, fibrin thrombuss. The degradation of fibrin is termed fibrinolysis....
, the major enzyme responsible for clot breakdown. Because it works on the clotting system, tPA is used in clinical medicine
Clinical Medicine

Clinical Medicine, subtitled Journal of the Royal College of Physicians, is a medical journal published bimonthly by the Royal College of Physicians in London....
 to treat stroke
Stroke

A stroke is the rapidly developing loss of brain function due to a disturbance in the blood supply to the brain. According to the National Stroke Association, a "stroke" occurs when a blood clot blocks and artery or a blood vessel breaks, interrupting blood flow to an area of the brain....
.

Function


Fibrinolysis
The classic role of tPA is in the clotting system. Specifically, tPA catalyzes the conversion of plasminogen into plasmin
Plasmin

Plasmin is an important enzyme present in blood that degrades many blood plasma proteins, most notable, fibrin thrombuss. The degradation of fibrin is termed fibrinolysis....
. It does so by cleaving the single-chained plasminogen into two chains. These two chains are linked by a disulfide bond
Disulfide bond

In chemistry, a disulfide bond is a single covalent bond derived from the coupling of thiol groups. The linkage is also called an SS-bond or disulfide bridge....
 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
Thrombosis

Thrombosis is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel is injured, the body uses platelets and fibrin to form a blood clot, because the first step in repairing it is to prevent loss of blood....
 or embolism
Embolism

In medicine, an embolism occurs when an object migrates from one part of the body and causes a blockage of a blood vessel in another part of the body....
.

Tissue plasminogen activator also plays a role in cell migration
Cell migration

Cell migration is a central process in the development and maintenance of multicellular organisms. Tissue formation during embryogenesis, wound healing and immune systems all require the orchestrated movement of cells in a particular direction to a specific location....
 and tissue remodeling.

Genetics


Tissue plasminogen activator is a protein
Protein

Proteins are organic compounds made of amino acids arranged in a linear chain and joined together by peptide bonds between the carboxyl and amino groups of adjacent amino acid Residue ....
 encoded by the PLAT gene
Gene

A gene is the basic unit of heredity in a living organism. All living things depend on genes. Genes hold the information to build and maintain their cell and pass genetic trait to offspring....
, which is located on chromosome 8. The primary transcript
Primary transcript

A primary transcript is an RNA molecule that has not yet undergone any post-transcriptional modification after its transcription . For example, a precursor mRNA is a primary transcript that becomes a messenger RNA after processing, and a primary microRNA transcript becomes a microRNA after processing....
 produced by this gene undergoes alternative splicing
Alternative splicing

Alternative splicing is the RNA splicing variation mechanism in which the exons of the primary gene transcript, the pre-mRNA, are separated and reconnected so as to produce alternative ribonucleotide arrangements....
, producing three distinct messenger RNA
Messenger RNA

Messenger ribonucleic acid is a molecule of RNA encoding a chemical "blueprint" for a protein product. mRNA is transcription from a DNA template, and carries coding information to the sites of protein synthesis: the ribosomes....
s.

Clinical applications

Recombinant
Recombinant

Recombinant may refer to :* Recombinant DNA - a form of artificial DNA* , offers healthcare providers and academic medical centers proven, leading-edge data warehousing and clinical intelligence solutions to deliver higher quality outcomes, accelerate personalized medicine, and lower costs....
 tPA is used in diseases that feature blood clots, such as pulmonary embolism
Pulmonary embolism

Pulmonary embolism is a blockage of the pulmonary artery or one of its branches, usually occurring when a deep vein thrombosis becomes dislodged from its site of formation and travels, or embolism, to the pulmonary artery blood supply of one of the lungs....
, myocardial infarction
Myocardial infarction

Myocardial infarction , commonly known as a heart attack, occurs when the Blood flow to part of the heart is interrupted. This is most commonly due to occlusion of a coronary artery following the rupture of a Vulnerable plaque, which is an unstable collection of lipids and white blood cells in the wall of an artery....
 and stroke
Stroke

A stroke is the rapidly developing loss of brain function due to a disturbance in the blood supply to the brain. According to the National Stroke Association, a "stroke" occurs when a blood clot blocks and artery or a blood vessel breaks, interrupting blood flow to an area of the brain....
. 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 stroke
Lacunar stroke

Lacunar stroke or lacunar infarct is a type of stroke that results from occlusion of one of the penetrating artery that provides blood to the brain's deep structures....
s. 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
Frostbite

Frostbite is the medical condition wherein localized damage is caused to skin and other biological tissue due to extreme cold.Frostbite is most likely to happen in body parts farthest from the heart and those with large exposed areas....
 that were treated with tPA had fewer amputations than those that were not.

See also

  • Thrombolysis
    Thrombolysis

    Thrombolysis is the breakdown of thrombosis by pharmacology means. It is colloquially referred to as clot busting for this reason. It works by stimulating fibrinolysis by plasmin through infusion of analogs of tissue plasminogen activator, the protein that normally activates plasmin....
  • Ultrasound-Enhanced Systemic Thrombolysis
    Ultrasound-Enhanced Systemic Thrombolysis

    Ultrasound-Enhanced Systemic Thrombolysis is a medical technology that utilizes Transcranial doppler to treat stroke-causing blood clots. It is thought that Transcranial doppler aimed at residual obstructive intracranial blood flow may help expose thrombi to tissue plasminogen activator or other Thrombolytic drug....


Further reading


External links

  • from the American Heart Association
    American Heart Association

    The American Heart Association is a non-profit organization in the United States that fosters appropriate Heart care in an effort to reduce disability and deaths caused by cardiovascular disease and stroke....
  • - Scientific American Magazine (August 2005)