Endothelial dysfunction following thrombolysis in vitro.
OBJECTIVE
Thrombolytic therapy is frequently used to manage vascular graft thrombosis. However, long-term patency after thrombolysis remains poor. The purpose of this study was to characterise the morphological and functional response of endothelial cells (EC) exposed to a thrombus and subsequently lytic therapy.


METHODS
Human EC were exposed to human whole blood thrombus for 2, 6, 12, and 24 h. The thrombus was lysed with urokinase. Cell morphology was studied with electron microscopy. Northern blot analyses were performed with human c-DNA probes for endothelin-1, thrombomodulin, tissue factor, tissue plasminogen activator, plasminogen activator inhibitor, and triose phosphate isomerase.


RESULTS
EC retraction occurred for each period of incubation. Thrombomodulin expression was increased 2.2-fold at 6 h and 2.4-fold at 24 h. t-PA expression 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 do not appear to become actively procoagulant. The increase in TM expression may reflect enhanced thromboresistance. However, EC retraction may be responsible for an increase thrombogenicity of saphenous vein graft after thrombosis and Urokinase therapy.
d'Audiffret
A
A
Department of Surgery, SUNY at Buffalo, Millard Fillmore Hospital, NY 14209, USA.
Soloway
P
P
Saadeh
R
R
Carty
C
C
Bush
P
P
Ricotta
J J
JJ
Dryjski
M
M
D002478:Cells, Cultured; D019332:Endothelin-1 / Q000032:analysis; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D006083:Graft Occlusion, Vascular / Q000188:drug therapy; D006801:Humans; D008855:Microscopy, Electron, Scanning; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis; D012501:Saphenous Vein; D015912:Thrombolytic Therapy / Q000009:adverse effects*; D018180:Thrombomodulin / Q000032:analysis; D013925:Thromboplastin / Q000032:analysis; D013927:Thrombosis / Q000188:drug therapy; D010959:Tissue Plasminogen Activator / Q000032:analysis; D014568:Urokinase-Type Plasminogen Activator / Q000009:adverse effects / Q000627:therapeutic use
D019332:Endothelin-1; D017395:Plasminogen Activator Inhibitor 1; D018180:Thrombomodulin; D013925:Thromboplastin; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator