Thrombolytic Therapy Targeting Alpha 2-Antiplasmin
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Article, see p 1011
Tissue plasminogen activator (tPA) has been used as a thrombolytic agent for many years based on its high fibrin specificity, which contributes to its safety in thrombolytic therapy.1,2 Despite the favorable results associated with tPA treatments, its use is limited to the first 4.5 hours after the onset of event, and the dosage is strictly restricted in stroke treatment to avoid brain injury and bleeding. Thus, novel thrombolytic agents providing more safe and effective thrombolysis are desired.3
Fibrinolytic system dissolves unnecessary and aged thrombi, as well as newly generated and overabundant thrombi that exceed current hemostatic requirements. Similar to the coagulation system, the fibrinolytic system is strictly regulated4 to help maintain blood flow to the periphery. To achieve this complicated task, several distinct regulatory systems operate at the plasminogen activation and fibrin degradation levels (Figure 1). At the level of plasminogen activation, plasminogen activator inhibitor type 1 (PAI-1) plays the most important role by regulating the activity of tPA,5,6 which is the main PA in the vasculature and the most frequently used PA for thrombolytic therapy.
Alpha 2-antiplasmin (α2AP) and thrombin activatable fibrinolysis inhibitor (TAFI) play major roles in fibrinolysis.4 Plasmin activity is inhibited by …