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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2009;29:1151.)
© 2009 American Heart Association, Inc.

History of Discovery

The Tissue-Type Plasminogen Activator Story

D. Collen; H.R. Lijnen

From the Center for Molecular and Vascular Biology, University of Leuven, Belgium.

Correspondence to D. Collen, Center for Molecular and Vascular Biology, University of Leuven, Campus Gasthuisberg, O & N 1, Herestraat 49 Box 911, B-3000 Leuven, Belgium. E-mail desire.collen{at}med.kuleuven.be

Milestones in the development of tissue-type plasminogen activator (t-PA) as a fibrin-specific thrombolytic agent include: purification of human t-PA from the culture fluid of the Bowes melanoma cell line, elucidation of the molecular basis of fibrin-specific plasminogen activation, first experimental animal models of thrombosis, first patient (renal allograft) treated with melanoma t-PA, pilot studies in patients with acute myocardial infarction, cloning and expression of recombinant t-PA providing sufficient amounts for large scale clinical use, and demonstration of its therapeutic benefit in large multicenter clinical trials.

Key Words: acute myocardial infarction • thrombolytic therapy • pharmacological reperfusion