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Targeting coagulation factor XII provides protection from pathological thrombosis in cerebral ischemia without interfering with hemostasis

Standard

Targeting coagulation factor XII provides protection from pathological thrombosis in cerebral ischemia without interfering with hemostasis. / Kleinschnitz, Christoph; Stoll, Guido; Bendszus, Martin; Schuh, Kai; Pauer, Hans-Ulrich; Burfeind, Peter; Renné, Christoph; Gailani, David; Nieswandt, Bernhard; Renné, Thomas.

in: J EXP MED, Jahrgang 203, Nr. 3, 20.03.2006, S. 513-8.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Kleinschnitz, C, Stoll, G, Bendszus, M, Schuh, K, Pauer, H-U, Burfeind, P, Renné, C, Gailani, D, Nieswandt, B & Renné, T 2006, 'Targeting coagulation factor XII provides protection from pathological thrombosis in cerebral ischemia without interfering with hemostasis', J EXP MED, Jg. 203, Nr. 3, S. 513-8. https://doi.org/10.1084/jem.20052458

APA

Kleinschnitz, C., Stoll, G., Bendszus, M., Schuh, K., Pauer, H-U., Burfeind, P., Renné, C., Gailani, D., Nieswandt, B., & Renné, T. (2006). Targeting coagulation factor XII provides protection from pathological thrombosis in cerebral ischemia without interfering with hemostasis. J EXP MED, 203(3), 513-8. https://doi.org/10.1084/jem.20052458

Vancouver

Kleinschnitz C, Stoll G, Bendszus M, Schuh K, Pauer H-U, Burfeind P et al. Targeting coagulation factor XII provides protection from pathological thrombosis in cerebral ischemia without interfering with hemostasis. J EXP MED. 2006 Mär 20;203(3):513-8. https://doi.org/10.1084/jem.20052458

Bibtex

@article{98733079bd494de58f7754deb59e1e1a,
title = "Targeting coagulation factor XII provides protection from pathological thrombosis in cerebral ischemia without interfering with hemostasis",
abstract = "Formation of fibrin is critical for limiting blood loss at a site of blood vessel injury (hemostasis), but may also contribute to vascular thrombosis. Hereditary deficiency of factor XII (FXII), the protease that triggers the intrinsic pathway of coagulation in vitro, is not associated with spontaneous or excessive injury-related bleeding, indicating FXII is not required for hemostasis. We demonstrate that deficiency or inhibition of FXII protects mice from ischemic brain injury. After transient middle cerebral artery occlusion, the volume of infarcted brain in FXII-deficient and FXII inhibitor-treated mice was substantially less than in wild-type controls, without an increase in infarct-associated hemorrhage. Targeting FXII reduced fibrin formation in ischemic vessels, and reconstitution of FXII-deficient mice with human FXII restored fibrin deposition. Mice deficient in the FXII substrate factor XI were similarly protected from vessel-occluding fibrin formation, suggesting that FXII contributes to pathologic clotting through the intrinsic pathway. These data demonstrate that some processes involved in pathologic thrombus formation are distinct from those required for normal hemostasis. As FXII appears to be instrumental in pathologic fibrin formation but dispensable for hemostasis, FXII inhibition may offer a selective and safe strategy for preventing stroke and other thromboembolic diseases.",
keywords = "Animals, Blood Coagulation Factor Inhibitors, Blood Vessels, Brain Ischemia, Factor XI Deficiency, Factor XII, Factor XII Deficiency, Female, Fibrin, Hemostasis, Male, Mice, Mice, Knockout, Thrombosis",
author = "Christoph Kleinschnitz and Guido Stoll and Martin Bendszus and Kai Schuh and Hans-Ulrich Pauer and Peter Burfeind and Christoph Renn{\'e} and David Gailani and Bernhard Nieswandt and Thomas Renn{\'e}",
year = "2006",
month = mar,
day = "20",
doi = "10.1084/jem.20052458",
language = "English",
volume = "203",
pages = "513--8",
journal = "J EXP MED",
issn = "0022-1007",
publisher = "Rockefeller University Press",
number = "3",

}

RIS

TY - JOUR

T1 - Targeting coagulation factor XII provides protection from pathological thrombosis in cerebral ischemia without interfering with hemostasis

AU - Kleinschnitz, Christoph

AU - Stoll, Guido

AU - Bendszus, Martin

AU - Schuh, Kai

AU - Pauer, Hans-Ulrich

AU - Burfeind, Peter

AU - Renné, Christoph

AU - Gailani, David

AU - Nieswandt, Bernhard

AU - Renné, Thomas

PY - 2006/3/20

Y1 - 2006/3/20

N2 - Formation of fibrin is critical for limiting blood loss at a site of blood vessel injury (hemostasis), but may also contribute to vascular thrombosis. Hereditary deficiency of factor XII (FXII), the protease that triggers the intrinsic pathway of coagulation in vitro, is not associated with spontaneous or excessive injury-related bleeding, indicating FXII is not required for hemostasis. We demonstrate that deficiency or inhibition of FXII protects mice from ischemic brain injury. After transient middle cerebral artery occlusion, the volume of infarcted brain in FXII-deficient and FXII inhibitor-treated mice was substantially less than in wild-type controls, without an increase in infarct-associated hemorrhage. Targeting FXII reduced fibrin formation in ischemic vessels, and reconstitution of FXII-deficient mice with human FXII restored fibrin deposition. Mice deficient in the FXII substrate factor XI were similarly protected from vessel-occluding fibrin formation, suggesting that FXII contributes to pathologic clotting through the intrinsic pathway. These data demonstrate that some processes involved in pathologic thrombus formation are distinct from those required for normal hemostasis. As FXII appears to be instrumental in pathologic fibrin formation but dispensable for hemostasis, FXII inhibition may offer a selective and safe strategy for preventing stroke and other thromboembolic diseases.

AB - Formation of fibrin is critical for limiting blood loss at a site of blood vessel injury (hemostasis), but may also contribute to vascular thrombosis. Hereditary deficiency of factor XII (FXII), the protease that triggers the intrinsic pathway of coagulation in vitro, is not associated with spontaneous or excessive injury-related bleeding, indicating FXII is not required for hemostasis. We demonstrate that deficiency or inhibition of FXII protects mice from ischemic brain injury. After transient middle cerebral artery occlusion, the volume of infarcted brain in FXII-deficient and FXII inhibitor-treated mice was substantially less than in wild-type controls, without an increase in infarct-associated hemorrhage. Targeting FXII reduced fibrin formation in ischemic vessels, and reconstitution of FXII-deficient mice with human FXII restored fibrin deposition. Mice deficient in the FXII substrate factor XI were similarly protected from vessel-occluding fibrin formation, suggesting that FXII contributes to pathologic clotting through the intrinsic pathway. These data demonstrate that some processes involved in pathologic thrombus formation are distinct from those required for normal hemostasis. As FXII appears to be instrumental in pathologic fibrin formation but dispensable for hemostasis, FXII inhibition may offer a selective and safe strategy for preventing stroke and other thromboembolic diseases.

KW - Animals

KW - Blood Coagulation Factor Inhibitors

KW - Blood Vessels

KW - Brain Ischemia

KW - Factor XI Deficiency

KW - Factor XII

KW - Factor XII Deficiency

KW - Female

KW - Fibrin

KW - Hemostasis

KW - Male

KW - Mice

KW - Mice, Knockout

KW - Thrombosis

U2 - 10.1084/jem.20052458

DO - 10.1084/jem.20052458

M3 - SCORING: Journal article

C2 - 16533887

VL - 203

SP - 513

EP - 518

JO - J EXP MED

JF - J EXP MED

SN - 0022-1007

IS - 3

ER -