Plasminogen activator inhibitor type-1 (part two): role for failure of thrombolytic therapy. PAI-1 resistance as a potential benefit for new fibrinolytic agents.
Rapid and sustained reperfusion of an occluded coronary artery is the goal of thrombolytic therapy in acute myocardial infarction. However, the clot-dissolving efficacy of fibrinolytic agents such as tissue-type plasminogen activator (t-PA) is limited, in vivo, in part by the action of plasminogen activator inhibitor type-1 (PAI-1). A new generation of fibrinolytic agents has been genetically engineered to have greater resistance to PAI-1 inhibition. This article reviews the pathophysiologic role of PAI-1 in failure of thrombolytic therapy and describes the advantages that PAI-1-resistance may confer upon fibrinolytic agents such as TNK-t-PA, the new fibrinolytic agent with the most powerful PAI-1 resistance.
Huber
K
K
Department of Cardiology, University of Vienna-General Hospital, Währinger Gürtel 18/20, A-1090 Vienna, Austria. kurt.huber@univie.ac.at
D000818:Animals; D015195:Drug Design; D005343:Fibrinolytic Agents / Q000737:chemistry / Q000627:therapeutic use; D006801:Humans; D023421:Models, Animal; D009203:Myocardial Infarction / Q000188:drug therapy; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism / Q000502:physiology*; D015202:Protein Engineering; D015912:Thrombolytic Therapy / Q000379:methods*; D010959:Tissue Plasminogen Activator / Q000737:chemistry / Q000627:therapeutic use; D017211:Treatment Failure
D005343:Fibrinolytic Agents; D017395:Plasminogen Activator Inhibitor 1; C104096:TNK-tissue plasminogen activator; D010959:Tissue Plasminogen Activator