Augmentation of plasminogen activator inhibitor type 1 activity in plasma by thrombosis and by thrombolysis.
Both activation of platelets and elevation of plasminogen activator inhibitor type 1 (PAI-1) activity in plasma have been associated with acute myocardial infarction. Growth factors from platelet alpha-granules have been shown to increase PAI-1 synthesis in liver and endothelial cells in culture. The present study was designed to determine whether activation of platelets in vivo increases PAI-1 activity in plasma, thereby potentially attenuating thrombolysis. Carotid arteries in rabbits were stimulated with transluminal anodal current to initiate thrombosis manifested initially by cyclic flow variations known to reflect platelet activation. Flow was monitored with Doppler flow probes. Plasma PAI-1 activity (mean +/- SEM) assayed spectrophotometrically increased from 6.8 +/- 0.8 arbitrary units (AU)/ml to a peak of 19.1 +/- 2.9 AU/ml (n = 15) 4.8 +/- 0.6 h after the onset of cyclic flow variations. The magnitude of peak PAI-1 values correlated closely with the frequency and duration of antecedent cyclic flow variations. Complete thrombotic occlusion did not elevate PAI-1 beyond that seen with severe, repetitive partial occlusions (18.7 +/- 4.6 vs. 19.6 +/- 3.8 AU/ml). However, when recanalization of completely occluded vessels was induced with tissue-type plasminogen activator (t-PA), plasma PAI-1 increased more markedly (from 5.6 +/- 0.7 to 112.8 +/- 22.3 AU/ml, n = 11), exceeding the increase after corresponding intervals in animals in which t-PA failed to induce recanalization (from 5.2 +/- 1.1 to 28.3 +/- 6.1 AU/ml, n = 6). Thus, activation of platelets accompanying thrombosis or thrombolysis, or both, markedly increases PAI-1 activity in plasma.(ABSTRACT TRUNCATED AT 250 WORDS)
Cardiovascular Division, Washington University, School of Medicine, St. Louis, Missouri 63110.
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Fujii
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Abendschein
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Sobel
D000818:Animals; D001783:Blood Flow Velocity; D004730:Endothelium, Vascular / Q000473:pathology; D015849:Plasminogen Inactivators / Q000097:blood*; D015539:Platelet Activation; D011817:Rabbits; D012044:Regression Analysis; D015912:Thrombolytic Therapy; D013927:Thrombosis / Q000097:blood* / Q000503:physiopathology; D010959:Tissue Plasminogen Activator / Q000494:pharmacology
D015849:Plasminogen Inactivators; D010959:Tissue Plasminogen Activator