title: The role of galectin-3 and galectin-3-binding protein in venous thrombosis.
abstract: Galectin-3-binding protein (gal3bp) and its receptor/ligand, galectin-3 (gal3), are secreted proteins that initiate signaling cascades in several diseases, and recent human proteomic data suggest they may play a role in venous thrombosis (VT). We hypothesized that gal3bp and gal3 may promote VT. Using a mouse stasis model of VT, we found that gal3bp and gal3 were localized on vein wall, red blood cells, platelets, and microparticles, whereas leukocytes expressed gal3 only. Gal3 was dramatically increased during early VT and gal3bp:gal3 colocalized in the leukocyte/endothelial cell interface, where leukocytes were partially attached to the vein wall. Thrombus size correlated with elevated gal3 and interleukin-6 (IL-6) vein wall levels. Recombinant gal3 promoted VT and increased vein wall IL-6 mRNA. Although recombinant gal3 restored the VT size in gal3(-/-) mice, it had no effect on IL6(-/-) mice, suggesting that gal3:gal3bp promotes VT through IL-6. Moreover, significantly fewer activated neutrophils were present in the gal3(-/-) vein walls. In a group of human patients, elevated circulating gal3bp correlated with acute VT. In conclusion, gal3bp:gal3 play a critical role in VT, likely via IL-6 and PMN-mediated thrombotic mechanisms, and may be a potential biomarker in human VT.
authors.affiliation: Department of Surgery, Section of Vascular Surgery, Conrad Jobst Vascular Research Laboratories, and Unit for Laboratory Animal Research, University of Michigan, Ann Arbor, MI.
authors.forename: Elise P
authors.initials: EP
authors.lastname: DeRoo
authors.affiliation: Department of Surgery, Section of Vascular Surgery, Conrad Jobst Vascular Research Laboratories, and Unit for Laboratory Animal Research, University of Michigan, Ann Arbor, MI.
authors.forename: Shirley K
authors.initials: SK
authors.lastname: Wrobleski
authors.affiliation: Department of Surgery, Section of Vascular Surgery, Conrad Jobst Vascular Research Laboratories, and Unit for Laboratory Animal Research, University of Michigan, Ann Arbor, MI.
authors.forename: Evelyn M
authors.initials: EM
authors.lastname: Shea
authors.affiliation: Department of Surgery, Section of Vascular Surgery, Conrad Jobst Vascular Research Laboratories, and Unit for Laboratory Animal Research, University of Michigan, Ann Arbor, MI.
authors.forename: Ramsey K
authors.initials: RK
authors.lastname: Al-Khalil
authors.affiliation: Department of Surgery, Section of Vascular Surgery, Conrad Jobst Vascular Research Laboratories, and Unit for Laboratory Animal Research, University of Michigan, Ann Arbor, MI.
authors.forename: Angela E
authors.initials: AE
authors.lastname: Hawley
authors.affiliation: Department of Surgery, Section of Vascular Surgery, Conrad Jobst Vascular Research Laboratories, and Unit for Laboratory Animal Research, University of Michigan, Ann Arbor, MI.
authors.forename: Peter K
authors.initials: PK
authors.lastname: Henke
authors.affiliation: Department of Surgery, Section of Vascular Surgery, Conrad Jobst Vascular Research Laboratories, and Unit for Laboratory Animal Research, University of Michigan, Ann Arbor, MI.
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Myers
authors.affiliation: Department of Surgery, Section of Vascular Surgery, Conrad Jobst Vascular Research Laboratories, and Unit for Laboratory Animal Research, University of Michigan, Ann Arbor, MI.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Wakefield
authors.affiliation: Department of Surgery, Section of Vascular Surgery, Conrad Jobst Vascular Research Laboratories, and Unit for Laboratory Animal Research, University of Michigan, Ann Arbor, MI.
authors.forename: Jose A
authors.initials: JA
authors.lastname: Diaz
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000097:blood; D015415:Biomarkers / Q000097:blood; D014408:Biomarkers, Tumor / Q000097:blood; D001792:Blood Platelets / Q000378:metabolism; D002352:Carrier Proteins / Q000097:blood; D002465:Cell Movement; D018932:Chemokine CCL2 / Q000378:metabolism; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism; D037502:Galectin 3 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D006023:Glycoproteins / Q000097:blood / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000097:blood / Q000235:genetics / Q000378:metabolism; D020246:Venous Thrombosis / Q000097:blood / Q000209:etiology / Q000378:metabolism*; D016326:Extracellular Matrix Proteins
chemical_list: D000951:Antigens, Neoplasm; D015415:Biomarkers; D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D018932:Chemokine CCL2; D037502:Galectin 3; D006023:Glycoproteins; D015850:Interleukin-6; D012333:RNA, Messenger; D011994:Recombinant Proteins; C491768:Ccl2 protein, mouse; C081856:LGALS3BP protein, human; D016326:Extracellular Matrix Proteins; C485095:Lgals3 protein, mouse; C082349:Ppicap protein, mouse