Defective thrombus formation in mice lacking coagulation factor XII
Standard
Defective thrombus formation in mice lacking coagulation factor XII. / Renné, Thomas; Pozgajová, Miroslava; Grüner, Sabine; Schuh, Kai; Pauer, Hans-Ulrich; Burfeind, Peter; Gailani, David; Nieswandt, Bernhard.
In: J EXP MED, Vol. 202, No. 2, 18.07.2005, p. 271-81.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Defective thrombus formation in mice lacking coagulation factor XII
AU - Renné, Thomas
AU - Pozgajová, Miroslava
AU - Grüner, Sabine
AU - Schuh, Kai
AU - Pauer, Hans-Ulrich
AU - Burfeind, Peter
AU - Gailani, David
AU - Nieswandt, Bernhard
PY - 2005/7/18
Y1 - 2005/7/18
N2 - Blood coagulation is thought to be initiated by plasma protease factor VIIa in complex with the membrane protein tissue factor. In contrast, coagulation factor XII (FXII)-mediated fibrin formation is not believed to play an important role for coagulation in vivo. We used FXII-deficient mice to study the contributions of FXII to thrombus formation in vivo. Intravital fluorescence microscopy and blood flow measurements in three distinct arterial beds revealed a severe defect in the formation and stabilization of platelet-rich occlusive thrombi. Although FXII-deficient mice do not experience spontaneous or excessive injury-related bleeding, they are protected against collagen- and epinephrine-induced thromboembolism. Infusion of human FXII into FXII-null mice restored injury-induced thrombus formation. These unexpected findings change the long-standing concept that the FXII-induced intrinsic coagulation pathway is not important for clotting in vivo. The results establish FXII as essential for thrombus formation, and identify FXII as a novel target for antithrombotic therapy.
AB - Blood coagulation is thought to be initiated by plasma protease factor VIIa in complex with the membrane protein tissue factor. In contrast, coagulation factor XII (FXII)-mediated fibrin formation is not believed to play an important role for coagulation in vivo. We used FXII-deficient mice to study the contributions of FXII to thrombus formation in vivo. Intravital fluorescence microscopy and blood flow measurements in three distinct arterial beds revealed a severe defect in the formation and stabilization of platelet-rich occlusive thrombi. Although FXII-deficient mice do not experience spontaneous or excessive injury-related bleeding, they are protected against collagen- and epinephrine-induced thromboembolism. Infusion of human FXII into FXII-null mice restored injury-induced thrombus formation. These unexpected findings change the long-standing concept that the FXII-induced intrinsic coagulation pathway is not important for clotting in vivo. The results establish FXII as essential for thrombus formation, and identify FXII as a novel target for antithrombotic therapy.
KW - Animals
KW - Blood Coagulation
KW - Collagen
KW - Epinephrine
KW - Factor VIIa
KW - Factor XII Deficiency
KW - Factor XIIa
KW - Hemorrhage
KW - Lung
KW - Mice
KW - Mice, Mutant Strains
KW - Platelet Aggregation
KW - Thromboembolism
KW - Vasoconstrictor Agents
U2 - 10.1084/jem.20050664
DO - 10.1084/jem.20050664
M3 - SCORING: Journal article
C2 - 16009717
VL - 202
SP - 271
EP - 281
JO - J EXP MED
JF - J EXP MED
SN - 0022-1007
IS - 2
ER -