Gardenia

Tissue plasminogen activator (abbreviated tPA or PLAT) is a protein involved in the breakdown of blood clots. It is a serine protease (EC3.4.21.68) found on endothelial cells, the cells that line the blood vessels. As an enzyme, it catalyzes the conversion of plasminogen toplasmin, the major enzyme responsible for clot breakdown. Because it works on the clotting system, tPA is used in clinical medicine to treat only embolic or thrombotic stroke. Use is contraindicated in hemorrhagic stroke and head trauma.

tPA may be manufactured using recombinant biotechnology techniques. tPA created this way may be referred to as recombinant tissue plasminogen activator (rtPA).

The classic role of tPA is in the clotting system. To be specific, tPA catalyzes the conversion ofplasminogen into plasmin. It does so by cleaving the single-chain 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 onchromosome 8. The primary transcript produced by this gene undergoes alternative splicing, producing three distinct messenger RNAs.

Clinical applications

tPA is used in diseases that feature blood clots, such as pulmonary embolism, myocardial infarction, and stroke, in a medical treatment calledthrombolysis. To be most effective in ischemic stroke, tPA must be administered as early as possible after the onset of symptoms. Protocol guidelines require its use intravenously within the first three hours of the event, after which its detriments may outweigh its benefits. They can either be administered systemically, in the case of acute myocardial...