Evaluation of the pro-angiogenic effect of factor XIII in heterotopic mouse heart allografts and FXIII-deficient mice

Rima Dardik, Jonathan Leor, Ehud Skutelsky, David Castel, Radka Holbova, Ginette Schiby, Aviv Shaish, Gerhard Dickneite, Joseph Loscalzo, Aida Inbal

Research output: Contribution to journalArticlepeer-review

Abstract

Thrombin-activated Factor XIII (FXllla), a plasma transglutaminase, stabilizes fibrin clots by crosslinking fibrin chains. FXIIIa was previously shown by us to exhibit proangiogenic activity associated with downregulation of thrombospondin-I,phosphorylation of vascular endothelial growth factor receptor 2 (VEGFR-2), and upregulation of c-Jun. In the current study, we evaluated the proangiogenic effect of FXIIla in two murine models: a neonatal heterotopic cardiac allograft model in normal mice, and a Matrigel plug model in FXIII-deficient mice. In the neonatal cardiac allograft model, the number of new vessels as well as graft viability (contractile performance) was significantly higher in FXllla-injected animals than in controls. A significant increase in the level of c-Jun mRNA and a significant decrease in the level of TSP-I mRNA were observed in heart allografts treated with FXIIIa. A marked decrease in TSP-I protein expression was observed within the endothelial cells of hearts treated with FXIIIa. In the Matrigel plug model, FXIII-deficient mice showed a significantly decreased number of new vessels compared to that of the control mice, and the number of vessels almost reached normal levels following addition of FXIIIa.The results of this study provide substantial in vivo evidence for the proangiogenic activity of FXIIIa.

Original languageEnglish
Pages (from-to)546-550
Number of pages5
JournalThrombosis and Haemostasis
Volume95
Issue number3
DOIs
StatePublished - Mar 2006

Keywords

  • Angiogenesis
  • Factor XIII
  • Thrombospondin-I

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