Recent Progresses in the Protein Engineering of Thrombolytic Agents

Arterial thrombosis is the underlying cause of a wide variety of cardiovascular diseases including myocardial infarction.All the currently used thrombolytic agents are plasminogen activators,which are very efficient in restoring the blood flow.They can convert plasminogen into plasmin and thus degrade fibrin.Despite the widespread use of established thrombolytic agents such as streptokinase,t\|PA and u\|PA,all these agents suffer from a number of inadequacies including resistance to reperfusion,occurrence of coronary reocclusion and bleeding complications.The quest continues for plasminogen activators with higher potency,specific thrombolytic activity,fibrin selectivity and longer half\|life time.The recent progress in the protein engineering of plasminogen activators,including t\|PA,u\|PA,streptokinase,staphylokinase and other novel plasminogen activators,was presented in this article.We can conclude that the new generation of thrombolytic agents showed considerable potential with regard to improving the efficacy of thrombolytic therapy,and these progresses were based on the detailed understanding of the relationship between structure and function of thrombolytic agents.However,the risk of intracranial bleeding remains problematic and need more researches on the modification of thrombolytic agents.