Inhibition of tissue plasminogen activator activity by aspirin in vivo and its relationship to levels of tissue plasminogen activator inhibitor antigen, plasminogen activator and their complexes.
The observation that aspirin inhibits the increment in tissue plasminogen activator (t-PA) activity induced by venous occlusion of the forearm became controversial with the publication of several nonconfirmatory studies. The current study was performed to confirm the original observation and determine the mechanism by which aspirin suppresses the incremental t-PA activity induced by venous occlusion. Aspirin (650 mg/d X 2) caused no change in resting levels of t-PA antigen (t-PA:Ag) or activity, plasminogen activator inhibitor 1 antigen (PAI-1:Ag), or activity or t-PA-PAI-1 complexes. In contrast, aspirin reduced the increments induced by venous occlusion as follows: t-PA:Ag by 45% (P = .001); t-PA activity (euglobulin lysis time, ELT) by 43% (P = .006); and t-PA activity (alpha 2-plasmin inhibitor-plasmin complexes, PIPC) by 41% (P = .003). The inhibition of incremental t-PA activity measured as ELT or PIPC was linearly correlated with the inhibition of incremental t-PA:Ag (respectively, r = .75, P less than .02; r = .67, P less than .05). Aspirin had no effect on the increment in PAI-1:Ag induced by venous occlusion, but similar to the effect on t-PA:Ag, aspirin induced a 51% inhibition of the increment in t-PA-PAI-1 complex formation. Aspirin did not alter the ability of alpha 2-plasmin inhibitor to bind plasmin, nor the ability of plasma to support the fibrin-catalyzed generation of plasmin by t-PA, nor the subsequent formation of PIPC. Aspirin inhibits the t-PA activity induced by venous occlusion primarily by inhibiting the release of t-PA antigen.
Levin
R I
RI
Division of Cardiology, New York University School of Medicine, NY.
Harpel
P C
PC
Harpel
J G
JG
Recht
P A
PA
D000933:Antifibrinolytic Agents / Q000378:metabolism*; D001241:Aspirin / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005341:Fibrinolysin / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D015849:Plasminogen Inactivators / Q000097:blood*; D010959:Tissue Plasminogen Activator / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000097:blood; D000979:alpha-2-Antiplasmin
D000933:Antifibrinolytic Agents; D015849:Plasminogen Inactivators; D000979:alpha-2-Antiplasmin; C037742:plasmin-plasmin inhibitor complex; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin; D001241:Aspirin