Fibrinolysis: Introduction
Introduction
Fibrinolysis is the process by which fibrin is removed from damaged blood vessels. Fibrinolysis is also important in tissue remodelling and repair after injury.
Key: t-PA - tissue plasminoge activator; u-PA - urinary plasminogen activator; XL-Fibrin - cross-linked fibrin; TAFI - Thrombin Activatable Fibrinolytic Inhibitor.
The components of the fibrinolytic pathway comprise:
| Protein | Function | Half-Life | Gene |
|---|---|---|---|
| Plasminogen [PLG] - is the precursor of plasmin, the active active serine protease that is involved in the breakdown of fibrin. Plasmin can also interact with other molecules e.g fibrinogen, factor V, VIII, |
PLG contains an active site serine that constitutes the active site serine protease of plasmin but in addition 5 kringle modules [so called because of their resemblance to a Scandinavian pastry, a Nordic variety of pretzel], 4 of which have lysine binding sites and it through these that plasminogen interacts with its substrates; its activators and its inhibitors. Cleavage of the Arg561-Val562 bond in PLG either by t-PA or u-PA converts the protein from an inactive zymogen to the active serine protease. |
50 hours | 6q27 |
| t-PA | A serine protease secreted constitutively by vascular endothelial cells. T-PA is the principal activator of PLG. T-PA has a shortly half-life of 2-3 minutes in plasma due to the presence of a potent inhibitor termed PAI-1. The affinity of t-PA for PLG increases significantly in the presence of a fibrin clot. Cleavage of t-PA from a single chain molecular to a two chain molecule is also associated with an increase in its enzymatic activity. |
2-3 minutes | 8p11.1 |
| u-PA | U-PA was first isolated from urine and from which it obtains it name. U-PA is an activator of PLG to plasmin and primarily involvd in extra-vascular remodelling and repair after tissue injury. |
2-3 minutes | 10q22 |
| PAI-1 | Major inhibitor of t-PA and u-PA. Secreted constitutively by vascular endothelial cells. Member of the SERPIN [serine protease inhibitor] superfamily of proteins. T-PA:PAI-1 complexes are removed by the liver. T-PA bound to a fibrin clot is relatively protected from inactivation by PAI-1 |
4-5 minutes | 7q22 |
| α2-antiplasmin [α2-Plasmin Inhibitor] |
The major inhibitor of Plasmin. Member of the SERPIN [serine protease inhibitor] superfamily of proteins. Cross-linked in the fibrin clot by FXIIIa and so renders the clot resistant to fibrinolysis |
72 hours | 17p13 |
| Fibrinogen | Converted by thrombin to fibrin and cross-linked to form an insoluble polymer by FXIIIa | 90 hours | 4q32 for all 3 chains |
| TAFI | TAFI removes the C-terminal lysines from plasmin and so removes the binding sites for both PLG and t-PA, | 10 minutes | 13q14 |
Data Interpretation
Click HERE to go to the Data Interpretation Exercises.