Impaired clot lysis by rt-PA catalyzed mini-plasminogen activation.
The fibrinolytic system contains a proenzyme plasminogen (Plg) which is converted to plasmin (Plm) by the action of Plg activators. Physiological Plg activators are: tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator. Plg was shown to be further cleaved by leukocyte elastase producing several fragments, one of which is called mini-plasminogen (mini-Plg) or neo-plasminogen Val442. In this paper we studied whether mini-Plg is able to produce clot lysis when it is activated by rt-PA in purified systems and in Plg depleted normal plasma. We found that mini-Plg clot lysis time was longer than that of Plg. Clot lysis times were 2.3 minutes +/- 0.06 for Plg and 9.8 minutes +/- 0.1 for mini-Plg. Mini-Plg is less efficient than Plg in producing clot lysis at all studied concentrations (0.1-1.2 microM). In Plg depleted normal human plasma mini-Plg is unable to produce complete clot lysis in presence of rt-PA. Although mini-Plg can be activated to mini-Plm by rt-PA, these results show that the activation process is insufficient to produce an efficient clot lysis.
Duboscq
C
C
Laboratorio de Hemostasia y Trombosis, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina.
Genoud
V
V
Parborell
M F
MF
Kordich
L C
LC
D005337:Fibrin / Q000378:metabolism / Q000494:pharmacology; D005341:Fibrinolysin / Q000378:metabolism; D005342:Fibrinolysis / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D010446:Peptide Fragments / Q000187:drug effects* / Q000378:metabolism*; D010958:Plasminogen / Q000187:drug effects* / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D010959:Tissue Plasminogen Activator / Q000378:metabolism / Q000494:pharmacology*
D010446:Peptide Fragments; D011994:Recombinant Proteins; C019493:miniplasmin; C044190:miniplasminogen; D005337:Fibrin; D010958:Plasminogen; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin