TY - JOUR
T1 - Evaluation of the pro-angiogenic effect of factor XIII in heterotopic mouse heart allografts and FXIII-deficient mice
AU - Dardik, Rima
AU - Leor, Jonathan
AU - Skutelsky, Ehud
AU - Castel, David
AU - Holbova, Radka
AU - Schiby, Ginette
AU - Shaish, Aviv
AU - Dickneite, Gerhard
AU - Loscalzo, Joseph
AU - Inbal, Aida
PY - 2006/3
Y1 - 2006/3
N2 - 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.
AB - 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.
KW - Angiogenesis
KW - Factor XIII
KW - Thrombospondin-I
UR - http://www.scopus.com/inward/record.url?scp=33645543811&partnerID=8YFLogxK
U2 - 10.1160/TH05-06-0409
DO - 10.1160/TH05-06-0409
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C2 - 16525585
AN - SCOPUS:33645543811
SN - 0340-6245
VL - 95
SP - 546
EP - 550
JO - Thrombosis and Haemostasis
JF - Thrombosis and Haemostasis
IS - 3
ER -
