Plasminogen activators (t-PA, u-PA)
Biochemistry
u-PA (urokinase) | t-PA | |
---|---|---|
Single-chain form | single-chain urokinase (sc u-PA), Prourokinase, inactive form | single-chain tissue-type plasminogen activator, sc t-PA |
Two-chain form | two-chain Urokinase (tc u-PA), Urokinase, active form | two-chain tissue-type plasminogen activator, tc t-PA |
Molecular mass | 54 000 D | 68 000 D |
Half-life | 5 - 10 minutes | 4 - 5 minutes |
Plasma concentration | 2 - 8 ng/ml | 5 ng/ml total t-PA antigen 1 ng/ml free t-PA antigen 0.5 IU/ml t-PA activity Note: Individual and circadian variations |
Synthesis | kidneys, lungs | endothelial cells |
Primary structure | 411 amino acids | 530 amino acids |
The most important plasminogen activator in plasma is t-PA. Similar to plasminogen, t-PA shows a high binding affinity to fibrin via specific binding sites. The originally weak activation capacity of t-PA is considerably accelerated in the presence of fibrin. In this way, fibrin bound plasminogen is preferentially activated. This results in the lysis of the fibrin clot from the inside. u-PA only plays a minor role as plasminogen activator in plasma. It is of importance in tissue transformation, cell migration and tumor metastasis in the extravasal space. Single-chain prourokinase is activated to the two-chain form by kallikrein.
Clinical significance
Patients showing a reduced release of t-PA following occlusion or DDAVP infusion are called "non-responders". They have an increased risk for thromboembolic complications such as venous or arterial occlusion, apoplexy and coronary diseases. Increased t-PA values are observed in stress, tumor diseases, liver transplantations and hepatic failure.
Indication
- Diagnosis of thrombophilia
- Suspected increase or decrease of fibrinolytic potential
Literature
- Meijer P et al. The use of Stabilyte plasma may cause changes in pH in the assay of some fibrinolysis analytes and might effect results. Fibrinolysis 10 (Suppl. 2), 155-157, 1996.
- Geppert A et al. Concentration of Endogenous t-PA Antigen in Coronary Artery Disease. Arterioscler Thromb Vasc Biol 18, 1634-1642, 1998.
- Roldán-Olarte M, García DC, Jiménez-Díaz M, Valdecantos PA, Miceli DC. In vivo and in vitro expression of the plasminogen activators and urokinase type plasminogen activator receptor (u-PAR) in the pig oviduct. Anim Reprod Sci. Dec 136(1-2), 90-9, 2012.
- Keller L, Hobohm C, Zeynalova S, Classen J, Baum P. Does treatment with t-PA increase the risk of developing epilepsy after stroke? J Neurol. Oct 262(10), 2364-72, 2015.
- Rosen S et al. Evaluation of a bioimmuno assay for t-PA activity and its relation to PAI-1 activity and antigen levels. Fibr Proteol 12, 340-346, 1998.
- Kluft C, Meijer P. Update 1996: Blood collection and handling procedures for assessment of plasminogen activators and inhibitors (Leiden Fibrinolysis Workshop), Fibrinolysis 10 (Suppl. 2) 171-179, 1996.