The
carboxypeptidase, TAFIa or CPU, is known to prolong plasma clot lysis by
tissue plasminogen activator (tPA) and to have a role in
thrombus stability in vivo. This current study examined lysis by
urokinase (uPA) and single chain
urokinase (scuPA) in addition to tPA. Further, we investigated the role of TAFIa in a model
thrombus system, in which thrombi are formed under conditions of flow. We show that human thrombi, formed in vivo, and model thrombi both contain TAFI. No effect of
thrombus TAFIa was observed in
thrombus lysis assays, except when thrombi were bathed in plasma, in which case addition of potato tuber
carboxypeptidase inhibitor (
CPI) resulted in doubling of the rate of lysis. TAFIa inhibited lysis of model thrombi and plasma clots by uPA, scuPA in addition to lysis by tPA. The effect of TAFIa was more evident at high concentrations of
plasminogen activator such as those used in
thrombolytic therapy. Addition of
plasminogen increased lysis and, in its presence, the enhancement by
CPI was smaller. Thus the action of TAFIa could be partially overcome by
plasminogen, whether lysis was by tPA, uPA or scuPA. This is consistent with TAFIa exerting its effect primarily through modifying the binding of
plasminogen to
fibrin and to a lesser extent through modification of the binding of tPA to
fibrin.