COX‐1+/−COX‐2−/− genotype in mice is associated with shortened time to carotid artery occlusion through increased PAI‐1

Autor: L. He, Terrence E. Riehl, S. Greco, Douglas M. Tollefsen, L. Zheng, William F. Stenson
Rok vydání: 2011
Předmět:
Zdroj: Journal of Thrombosis and Haemostasis. 9:350-360
ISSN: 1538-7836
DOI: 10.1111/j.1538-7836.2010.04156.x
Popis: Summary. Background: We found a high incidence of thrombotic deaths in COX-1+/−COX-2−/− mice and sought to define the mechanism of these events. The cyclooxygenase products thromboxane A2 and prostacyclin are important in the regulation of coagulation but their role in fibrinolysis is largely unexplored. PAI-1 blocks fibrinolysis by inhibiting plasminogen activator. Aim: Our objective was to explain the mechanism of increased thrombosis associated with the COX-1+/−COX-2−/− genotype. Methods: Carotid artery occlusion times were measured after photochemical injury. PAI-1 levels were measured in the plasma by ELISA. PAI-1 levels in the aorta were measured by RT-PCR and Western blotting. Urinary metabolites of Thromboxane A2 and prostacyclin were measured by ELISA. Results: The COX-1+/−COX-2−/− genotype is associated with a decreased time to occlusion in the carotid artery thrombosis model (30 ± 5 minutes vs 60 ± minutes in wild type, p
Databáze: OpenAIRE