Effect of PAI-1 levels on the molar concentrations of active tissue plasminogen activator (t-PA) and t-PA/PAI-1 complex in plasma.
We determined the in vivo molar concentrations of active tissue plasminogen activator (t-PA), active plasminogen activator inhibitor type 1 (PAI-1), and t-PA/PAI-1 complex. t-PA activity was measured in plasma stabilized by immediate acidification. PAI-1 activity and t-PA/PAI-1 complex antigen were measured in citrated plasma; these measurements were corrected for the loss in PAI-1 activity and increase in complex that occurs in unacidified plasma samples due to the continued reaction between t-PA and PAI-1 after the sample was drawn. To convert t-PA and PAI-1 activity measurements into molar concentrations we determined the specific molar activity of t-PA and PAI-1 in vivo: 4.48 x 10(13) IU/mol. Of 72 subjects studied, 13 had less than 150 pmol/L active PAI-1; in these individuals 33% +/- 21% of their t-PA was active and the molar ratio of active t-PA to active PAI-1 was 0.20 +/- 0.13. In the 11 subjects with greater than 500 pmol/L active PAI-1, 1.5% = 1.1% of the t-PA was active and the molar ratio of active t-PA to active PAI-1 was 0.0043 +/- 0.0036. Overall, the fraction of active t-PA declined exponentially as a function of the active PAI-1 concentration. During the day, the percentage of total t-PA that was active increased from 12% at 8:00 AM to 31% at 8:00 PM, while the molar ratio of active t-PA to active PAI-1 increased from 0.05 to 0.22 from morning to evening (n = 12).
Chandler
W L
WL
Department of Laboratory Medicine, University of Washington, Seattle, WA 98195.
Trimble
S L
SL
Loo
S C
SC
Mornin
D
D
D000991:Antithrombins / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005342:Fibrinolysis; D006801:Humans; D007700:Kinetics; D046911:Macromolecular Substances; D010449:Peptide Mapping; D015849:Plasminogen Inactivators / Q000097:blood* / Q000302:isolation & purification; D013379:Substrate Specificity; D010959:Tissue Plasminogen Activator / Q000097:blood* / Q000302:isolation & purification
D000991:Antithrombins; D046911:Macromolecular Substances; D015849:Plasminogen Inactivators; D010959:Tissue Plasminogen Activator