title: α(1,3)-Fucosyltransferases FUT4 and FUT7 control murine susceptibility to thrombosis.
abstract: The α(1,3)-fucosyltransferases, types IV and VII (FUT4 and FUT7, respectively), are required for the synthesis of functional selectin-type leukocyte adhesion molecule ligands. The selectins and their ligands modulate leukocyte trafficking, and P-selectin and its ligand, P-selectin glycoprotein ligand-1, can modulate hemostasis and thrombosis. Regulation of thrombosis by FUT4 and/or FUT7 activity was examined in mouse models of carotid artery thrombosis and collagen/epinephrine-induced thromboembolism. Mice lacking both FUT4 and FUT7 (Fut(-/-) mice) had a shorter time to occlusive thrombus formation in the injured carotid artery and a higher mortality due to collagen/epinephrine-induced pulmonary thromboemboli. Mice lacking P-selectin or P-selectin glycoprotein ligand-1 did not have a prothrombotic phenotype. Whole blood platelet aggregation was enhanced, and plasma fibrinogen content, clot weight, and clot strength were increased in Fut(-/-) mice, and in vitro clot lysis was reduced compared with wild type. Fut4(-/-), but not Fut7(-/-), mice had increased pulmonary thromboembolism-induced mortality and decreased thromboemboli dissolution in vivo. These data show that FUT4 and FUT7 activity regulates thrombosis in a P-selectin- and P-selectin glycoprotein ligand-1-independent manner and suggest that FUT4 activity is important for thrombolysis.
authors.affiliation: Department of Pathology and Laboratory Medicine and the McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7525, USA.
authors.forename: Huili
authors.initials: H
authors.lastname: Wang
authors.forename: Maria
authors.initials: M
authors.lastname: Morales-Levy
authors.forename: Jason
authors.initials: J
authors.lastname: Rose
authors.forename: Lantz C
authors.initials: LC
authors.lastname: Mackey
authors.forename: Peter
authors.initials: P
authors.lastname: Bodary
authors.forename: Daniel
authors.initials: D
authors.lastname: Eitzman
authors.forename: Jonathon W
authors.initials: JW
authors.lastname: Homeister
mesh_terms: D000818:Animals; D001777:Blood Coagulation / Q000502:physiology; D002341:Carotid Artery Thrombosis / Q000097:blood / Q000503:physiopathology*; D004198:Disease Susceptibility; D005337:Fibrin / Q000502:physiology; D005340:Fibrinogen / Q000378:metabolism; D005342:Fibrinolysis / Q000502:physiology; D005647:Fucosyltransferases / Q000172:deficiency / Q000502:physiology*; D053208:Kaplan-Meier Estimate; D051379:Mice; D018345:Mice, Knockout; D010314:Partial Thromboplastin Time; D010974:Platelet Aggregation / Q000502:physiology; D011517:Prothrombin Time; D011655:Pulmonary Embolism / Q000097:blood / Q000503:physiopathology*; D013917:Thrombin / Q000096:biosynthesis; D013997:Time Factors
chemical_list: D005337:Fibrin; D005340:Fibrinogen; D005647:Fucosyltransferases; C541914:Fut4 protein, mouse; C514210:fucosyltransferase VII, mouse; D013917:Thrombin
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