IntechOpen Fibrinolysis - Past, Present and Future (Biochemistry)

Fibrinolysis, the process of breaking down the fibrin network, was reported in 1925 by Fischer, who demonstrated that explants of virally induced chicken tumors rapidly caused lysis of plasma clots, whereas explants of normal tissue did not. This observation provided evidence for the importance of fibrinolysis in cancer. Then, in 1933, Tillett and Garner observed the liquefaction of a fibrin clot by the plasma of many patients who had recovered from acute hemolytic streptococcal infections. These investigators showed that broth cultures of hemolytic streptococci derived from patients could rapidly liquefy normal human fibrin clots. This suggested that fibrinolysis might play a key role in homeostasis, although its regulation mechanism was unknown. Fibrinolysis is now known to be regulated by four components, namely the plasminogen activators that function to convert plasminogen into plasmin to initiate fibrin degradation, such as tissue-type and urokinase-type plasminogen activators, the plasminogen activator inhibitors that block the plasminogen activators, the plasmin inhibitors such as alpha2-antiplasmin, and finally the enzymes that block plasminogen binding sites on fibrin or the endothelial cell surface, such as the thrombin activatable fibrinolysis inhibitor. Originally, fibrinolysis was thought to be only responsible for promoting vascular patency, the failure of which resulted in myocardial infarction and stroke. However, recent studies from multiple laboratories have identified the key role of fibrinolysis in a host of physiological and pathophysiological processes. Most recently, fibrinolysis has been suggested to play a role in forming the premetastatic niche, a hospitable site for future metastases in distal tissues, which is formed by secretions from the primary tumor before the departure of metastatic cancer cells. This book explores the multifaceted and intriguing role of fibrinolysis in several processes, including cancer, cardiovascular disease, neuroinflammation, and infection. The latest advances in fibrinolytic therapies are also discussed, which illustrates the complexity and depth of the field.