These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Enhanced fibrinolytic potential in mice with combined homozygous deficiency of alpha2-antiplasmin and PAI-1.
    Author: Dewerchin M, Collen D, Lijnen HR.
    Journal: Thromb Haemost; 2001 Aug; 86(2):640-6. PubMed ID: 11522016.
    Abstract:
    Alpha2-antiplasmin (alpha2-AP) and plasminogen activator inhibitor-1 (PAI-1) are the main physiological inhibitors of the plasminogen/plasmin system in mammalian plasma. In the present study, the relative importance of both inhibitors was evaluated with the use of mice with single or combined deficiency of alpha2-AP and PAI-1 in the same genetic background. Mice with combined deficiency (alpha2-AP-/-:PAI-1-/-) are viable, develop normally and are fertile. After amputation of the tail, bleeding times are prolonged (>15 min) in alpha2-AP-/-: PAI-1-/- mice, as compared to double wild-type or single deficient mice (4.6 to 10 min). Spontaneous lysis after 4 h of intravenously injected 125I-fibrin labeled plasma clots is significantly higher in mice with alpha2-AP deficiency both in the PAI-1+/+ background (89+/-2% versus 42+/-3%; p = 0.002) and in the PAI-1-/- background (83+/-4% versus 53+/-5%; p = 0.002). PAI-1 deletion in the alpha2-AP+/+ or alpha2-AP-/- background, however, has no significant effect (p = 0.13 or 0.18, respectively). Four hours after endotoxin injection, fibrin deposition in the kidneys is not significantly affected by PAI-1 deletion in mice with alpha2-AP+/+ or alpha2-AP-/- background (p = 0.07 and 0.19, respectively). In contrast, alpha2-AP deletion causes significantly reduced fibrin deposition in the PAI-1+/+ background (p = 0.01). Endotoxin injection causes a dramatic increase in PAI-1 antigen levels in kidney extracts of PAI-1+/+ animals, without effect on alpha2-AP levels. Taken together, these data indicate that the higher endogenous fibrinolytic capacity observed in mice with combined deficiency is mainly due to the lack of alpha2-AP and suggest a less important role for PAI-1.
    [Abstract] [Full Text] [Related] [New Search]