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Annexin II regulates fibrin homeostasis and neoangiogenesis in vivo.

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

Pubmed ID: 14702107


  • Ling Q
  • Jacovina AT
  • Deora A
  • Febbraio M
  • Simantov R
  • Silverstein RL
  • Hempstead B
  • Mark WH
  • Hajjar KA


The Journal of clinical investigation

Publication Data

January 31, 2004

Associated Grants

  • Agency: NHLBI NIH HHS, Id: HL07423
  • Agency: NHLBI NIH HHS, Id: HL42493
  • Agency: NHLBI NIH HHS, Id: HL46403
  • Agency: NHLBI NIH HHS, Id: HL67839

Mesh Terms

  • Animals
  • Annexin A2
  • Aorta
  • Cell Movement
  • Cells, Cultured
  • Collagen
  • Endothelium, Vascular
  • Fibrin
  • Homeostasis
  • Kinetics
  • Matrix Metalloproteinases
  • Mice
  • Mice, Knockout
  • Muscle, Smooth, Vascular
  • Neovascularization, Pathologic
  • Organ Specificity
  • Vascular Endothelial Growth Factor A