Annexin II regulates fibrin homeostasis and neoangiogenesis in vivo

摘要: A central tenet of fibrinolysis is that tissue plasminogen activator-dependent (t-PA- dependent) conversion to active plasmin requires the presence cofactor/substrate fibrin. However, previous in vitro studies have suggested endothelial cell surface protein annexin II can stimulate t-PA-mediated activation complete absence Here, homozygous II-null mice displayed deposition fibrin microvasculature and incomplete clearance injury-induced arterial thrombi. While these animals demonstrated normal lysis a fibrin-containing plasma clot, t-PA-dependent generation at was markedly deficient. Directed migration cells through collagen lattices also reduced, an peptide mimicking sequences necessary for t-PA binding blocked invasion Matrigel implants wild-type mice. In addition, II-deficient diminished neovascularization fibroblast growth factor-stimulated cornea oxygen-primed neonatal retina. Capillary sprouting from aortic ring explants reduced association with severe impairment metalloproteinase-9 -13. These data establish as regulator reveal impaired fibrinolytic activity constitutes barrier effective neoangiogenesis.