AMYLOID-BETA PEPTIDES STIMULATE TISSUE-TYPE PLASMINOGEN-ACTIVATOR BUTNOT RECOMBINANT PROUROKINASE

Tissue-type plasminogen activator (rt-PA) and prourokinase (rscu-PA) h ave been tested with respect to the influence of amyloid ss peptides o n plasminogen activation which was monitored by cleavage of the chromo genic plasmin substrate S-2251. It was shown that rt-PA is stimulated by amyloid ss peptides at concentrations of 10 mu g/ml in contrast to prourokinase, which does not alter its catalytic properties in presenc e of amyloid ss peptides. The stimulation of rt-PA can be inhibited by tranexamic acid indicating a molecular mode of stimulation similar to the fibrin mediated stimulation of rt-PA. Haemorrhagic bleeding is on e of the most severe disorders which may occur during fibrinolytic tre atment of myocardial infarction. The analysis of the data from the lar ge GUSTO trial revealed that the incidence of primary intracerebral ha emorrhage is 0.70 % (n = 10376) after treatment with tissue-type plasm inogen activator (rt-PA) and about 0.57 % (n = 10393) after applicatio n of streptokinase (1). Both treatment groups received intravenous hep arin. The significant increase of haemorhagic bleeding observed with r t-PA was suggested to be specific for fibrin-dependent plasminogen act ivators (1). In contrast to prourokinase and urokinase, rt-PA binds vi a its finger and kringle 2 domain to fibrin (2) which results in an in creased plasminogen-activating activity (3). A recent report provides evidence that rt-PA is also stimulated by Alzheimer amyloid ss (A ss)- peptides and this effect was suggested to be an explanation for lethal intracerebral haemorrhages observed during therapy with rt-PA (4). Co pyright (C) 1997 Elsevier Science Ltd.