Thrombotic phenotype of mice with a combined deficiency in plasminogen activator inhibitor 1 and vitronectin.
OBJECTIVE
The role of vitronectin (VN) in thrombosis is not fully understood, primarily because this adhesive glycoprotein not only stabilizes plasminogen activator inhibitor 1 (PAI-1) and thus protects fibrin from premature lysis, but also because it binds to platelet integrins and may influence platelet aggregation. The absence of quantitative approaches to characterize the thrombi formed in animal models under different conditions further complicates this analysis.


METHODS
In this report, we describe a more comprehensive approach to assess the stability of thrombi formed in mice deficient in PAI-1 (PAI-1(-/-)), VN (VN(-/-)) or both (PAI-1(-/-)/VN(-/-)).


RESULTS
We observed that all deficient mice developed unstable thrombi compared with wild type (WT) mice. Thus, only 31% of the thrombi formed in WT mice were unstable compared with 74% of PAI-1(-/-), 80% of VN(-/-), and 87% of PAI-1(-/-)/VN(-/-) mice. In this regard, the average number of emboli per WT mouse was significantly lower (0.55) compared with VN(-/-) (2.66), PAI-1(-/-) (2.1), and VN(-/-)/PAI-1(-/-) (2.35) mice. Finally, the total duration of complete vascular occlusion was higher and the rate of vascular patency was lower in the WT mice compared with the deficient mice.


CONCLUSIONS
Taken together, these observations indicate that the thrombotic phenotype of mice with a combined deficiency in PAI-1 and VN does not differ significantly from the phenotype of mice with deficiencies in only PAI-1 or VN. This observation suggests that PAI-1 and VN may influence thrombus stability by regulating a common pathway.
Koschnick
S
S
Department of Cell Biology, The Scripps Research Institute, La Jolla, CA, USA.
Konstantinides
S
S
Schäfer
K
K
Crain
K
K
Loskutoff
D J
DJ
D000818:Animals; D002712:Chlorides; D005290:Ferric Compounds; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D017395:Plasminogen Activator Inhibitor 1 / Q000172:deficiency* / Q000502:physiology; D013927:Thrombosis / Q000139:chemically induced / Q000209:etiology*; D013997:Time Factors; D014654:Vascular Patency; D019096:Vitronectin / Q000172:deficiency* / Q000502:physiology
D002712:Chlorides; D005290:Ferric Compounds; D017395:Plasminogen Activator Inhibitor 1; D019096:Vitronectin; C024555:ferric chloride