Endothelial dysfunction following thrombolysis in vitro

Objectives: thrombolytic therapy is frequently used to manage vascular graf t thrombosis. However, long-term patency after thrombolysis remains pear. T he purpose of this study was to characterise the morphological and function al response of endothelial cells (EC) exposed to a thrombus and subsequentl y lytic therapy. Methods: human EC were exposed to human whole blood thrombus for 2, 6, 12, and 24 h. The thrombus teas lysed with urokinase. Cell morphology was studi ed with electron microscopy. Northern blot analyses were performed with hum an c-DNA probes for endothelin-1, thrombomodulin, tissue factor, tissue pla sminogen activator, plasminogen activator inhibitor, and triose phosphate i somerase. Results: EC retraction occurred for each period of incubation. Thrombomodul in expression was increased 2.2-fold at 6 it and 2.4-fold at 24 h. t-PA exp ression was depressed proportionally to the duration of thrombus exposure. PAI and TF expression transiently increased 1.5-fold at 2 h of exposure and returned to baseline at 6 h. Endothelin expression remained unchanged. Conclusions: except for a transient increase in TF expression and reversal of the tPA/PAI ratio, EC exposed to thrombus no nor appear to become active ly procoagulant. The increase in TM expression may reflect enhanced thrombo resistance. However, EC retraction may be responsible for an increase throm bogenicity of saphenous vein graft after thrombosis and Urokinase therapy.