Role of coagulation factors in cerebral venous sinus and cerebral microvascular thrombosis. 2010

Mutsumi Nagai, and Cigdem Erkuran Yilmaz, and Daniel Kirchhofer, and Charles T Esmon, and Nigel Mackman, and D Neil Granger
Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130, USA.

OBJECTIVE The objective of this study was to define the relative contributions of three major pro- and anti-coagulation pathways (heparin-antithrombin, protein C, and tissue factor (TF)) in the thrombogenic responses that occur in large and small vessels of the brain. METHODS Cerebral venous sinus thrombosis was induced by topical application of FeCl3 on the superior sagittal sinus, while photoactivation of fluorescein was used to induce thrombus formation in cerebral microvessels. Heparin, activated protein C (APC), and antibodies to either APC or TF were used to assess thrombogenesis in wild-type mice. Mutant mice that overexpress the endothelial protein C receptor (EPCR-tg) or with TF deficiency in Tie2-expressing endothelial cells (LTFE) were also used. RESULTS Thrombus formation in the superior sagittal sinus of wild-type mice was attenuated by heparin and in EPCR-tg mice, while treatment with the APC antibodies enhanced thrombogenesis. Arteriolar thrombosis was largely unresponsive to the interventions studied. However, in cerebral venules, thrombosis was inhibited by heparin and in EPCR-tg mice. TF antibody treatment also inhibited venular thrombosis, with a similar attenuation noted in LTFE mice. CONCLUSIONS Thrombin promotes while the APC pathway blunts thrombus formation in an experimental model of cerebral venous sinus thrombosis. TF involvement is more evident in cerebral microvascular thrombogenesis, with endothelial cell-associated TF mediating this response in venules, but not arterioles.

UI MeSH Term Description Entries
D008297 Male Males
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D008822 Mice, Transgenic Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN. Transgenic Mice,Founder Mice, Transgenic,Mouse, Founder, Transgenic,Mouse, Transgenic,Mice, Transgenic Founder,Transgenic Founder Mice,Transgenic Mouse
D011486 Protein C A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation.
D011956 Receptors, Cell Surface Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands. Cell Surface Receptor,Cell Surface Receptors,Hormone Receptors, Cell Surface,Receptors, Endogenous Substances,Cell Surface Hormone Receptors,Endogenous Substances Receptors,Receptor, Cell Surface,Surface Receptor, Cell
D001779 Blood Coagulation Factors Endogenous substances, usually proteins, that are involved in the blood coagulation process. Clotting Factor,Coagulation Factors,Blood Coagulation Factor,Clotting Factors,Coagulation Factor,Coagulation Factor, Blood,Coagulation Factors, Blood,Factor, Coagulation,Factors, Coagulation,Factor, Blood Coagulation,Factor, Clotting,Factors, Blood Coagulation,Factors, Clotting
D002712 Chlorides Inorganic compounds derived from hydrochloric acid that contain the Cl- ion. Chloride,Chloride Ion Level,Ion Level, Chloride,Level, Chloride Ion
D003392 Cranial Sinuses Large endothelium-lined venous channels situated between the two layers of DURA MATER, the endosteal and the meningeal layers. They are devoid of valves and are parts of the venous system of dura mater. Major cranial sinuses include a postero-superior group (such as superior sagittal, inferior sagittal, straight, transverse, and occipital) and an antero-inferior group (such as cavernous, petrosal, and basilar plexus). Cranial Venous Sinuses,Intracranial Sinuses,Sinuses, Cranial,Sinuses, Cranial Venous,Sinuses, Intracranial,Venous Sinuses, Cranial
D003911 Dextrans A group of glucose polymers made by certain bacteria. Dextrans are used therapeutically as plasma volume expanders and anticoagulants. They are also commonly used in biological experimentation and in industry for a wide variety of purposes. Dextran,Dextran 40,Dextran 40000,Dextran 70,Dextran 75,Dextran 80,Dextran B-1355,Dextran B-1355-S,Dextran B1355,Dextran B512,Dextran Derivatives,Dextran M 70,Dextran T 70,Dextran T-40,Dextran T-500,Hemodex,Hyskon,Infukoll,Macrodex,Polyglucin,Promit,Rheodextran,Rheoisodex,Rheomacrodex,Rheopolyglucin,Rondex,Saviosol,Dextran B 1355,Dextran B 1355 S,Dextran T 40,Dextran T 500
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal

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