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Thromb Haemost 2006; 95(03): 546-550
DOI: 10.1160/TH05-06-0409
Animal Models
Schattauer GmbH

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

Rima Dardik
1   Institute of Thrombosis and Hemostasis, Tel Hashomer, and Sackler Faculty of Medicine, Tel Aviv University, Israel
,
Jonathan Leor
2   Neufeld Cardiac Research Institute, Tel Hashomer, and Sackler Faculty of Medicine, Tel Aviv University, Israel
,
Ehud Skutelsky
3   Institutes of Pathology, Tel Hashomer, and Sackler Faculty of Medicine, Tel Aviv University, Israel
,
David Castel
2   Neufeld Cardiac Research Institute, Tel Hashomer, and Sackler Faculty of Medicine, Tel Aviv University, Israel
,
Radka Holbova
2   Neufeld Cardiac Research Institute, Tel Hashomer, and Sackler Faculty of Medicine, Tel Aviv University, Israel
,
Ginette Schiby
3   Institutes of Pathology, Tel Hashomer, and Sackler Faculty of Medicine, Tel Aviv University, Israel
,
Aviv Shaish
4   Lipid and Atherosclerosis Research, Sheba Medical Center, Tel Hashomer, and Sackler Faculty of Medicine, Tel Aviv University, Israel
,
Gerhard Dickneite
5   Pharmacology and Toxicology, ZLB-Behring, Marburg, Germany
,
Joseph Loscalzo
6   Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachussets, USA
,
Aida Inbal
1   Institute of Thrombosis and Hemostasis, Tel Hashomer, and Sackler Faculty of Medicine, Tel Aviv University, Israel
› Author Affiliations
Further Information

Publication History

Received 11 June 2005

Accepted after revision 22 February 2005

Publication Date:
29 November 2017 (online)

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Summary

Thrombin-activated Factor XIII (FXIIIa),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-1, 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 FXIIIa 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 FXIIIa-injected animals than in controls. A significant increase in the level of c-Jun mRNA and a significant decrease in the level of TSP-1 mRNA were observed in heart allografts treated with FXIIIa. A marked decrease in TSP-1 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.

Keywords

Angiogenesis - factor XIII - thrombospondin-1
 

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