title: The role of platelet and endothelial GARP in thrombosis and hemostasis.
abstract: BACKGROUND
  Glycoprotein-A Repetitions Predominant protein (GARP or LRRC32) is present on among others human platelets and endothelial cells. Evidence for its involvement in thrombus formation was suggested by full knockout of GARP in zebrafish.
  
  
  OBJECTIVE
  To evaluate the role of GARP in platelet physiology and in thrombus formation using platelet and endothelial conditional GARP knock out mice.
  
  
  METHODS
  Platelet and endothelial specific GARP knockout mice were generated using the Cre-loxP recombination system. The function of platelets without GARP was measured by flow cytometry, spreading analysis and aggregometry using PAR4-activating peptide and collagen related peptide. Additionally, clot retraction and collagen-induced platelet adhesion and aggregation under flow were analyzed. Finally, in vivo tail bleeding time, occlusion time of the mesenteric and carotid artery after FeCl3-induced thrombosis were determined in platelet and endothelial specific GARP knock out mice.
  
  
  RESULTS
  Platelet specific GARP knockout mice had normal surface GPIb, GPVI and integrin αIIb glycoprotein expression. Although GARP expression was increased upon platelet activation, platelets without GARP displayed normal agonist induced activation, spreading on fibrinogen and aggregation responses. Furthermore, absence of GARP on platelets did not influence clot retraction and had no impact on thrombus formation on collagen-coated surfaces under flow. In line with this, neither the tail bleeding time nor the occlusion time in the carotid- and mesenteric artery after FeCl3-induced thrombus formation in platelet or endothelial specific GARP knock out mice were affected.
  
  
  CONCLUSIONS
  Evidence is provided that platelet and endothelial GARP are not important in hemostasis and thrombosis in mice.
authors.affiliation: Laboratory for Thrombosis Research, IRF Life Sciences, KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium.
authors.forename: Elien
authors.initials: E
authors.lastname: Vermeersch
authors.affiliation: Laboratory for Thrombosis Research, IRF Life Sciences, KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium.
authors.forename: Frederik
authors.initials: F
authors.lastname: Denorme
authors.affiliation: Laboratory for Thrombosis Research, IRF Life Sciences, KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium.
authors.forename: Wim
authors.initials: W
authors.lastname: Maes
authors.affiliation: Laboratory for Thrombosis Research, IRF Life Sciences, KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium.
authors.forename: Simon F
authors.initials: SF
authors.lastname: De Meyer
authors.affiliation: Laboratory for Thrombosis Research, IRF Life Sciences, KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium.
authors.forename: Karen
authors.initials: K
authors.lastname: Vanhoorelbeke
authors.affiliation: Laboratory of Immunology, National Institute of Allergy and infectious Diseases, Bethesda, MD, United States of America.
authors.forename: Justin
authors.initials: J
authors.lastname: Edwards
authors.affiliation: Laboratory of Immunology, National Institute of Allergy and infectious Diseases, Bethesda, MD, United States of America.
authors.forename: Ethan M
authors.initials: EM
authors.lastname: Shevach
authors.affiliation: The Jackson Laboratory for Genomic Medicine, Farmington, CT, United States of America.
authors.forename: Derya
authors.initials: D
authors.lastname: Unutmaz
authors.affiliation: Chromatin Biochemistry Research Group, Combined Program on Microbiology and Immunology Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
authors.forename: Hodaka
authors.initials: H
authors.lastname: Fujii
authors.affiliation: Laboratory for Thrombosis Research, IRF Life Sciences, KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium.
authors.forename: Hans
authors.initials: H
authors.lastname: Deckmyn
authors.affiliation: Laboratory for Thrombosis Research, IRF Life Sciences, KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium.
authors.forename: Claudia
authors.initials: C
authors.lastname: Tersteeg
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D003094:Collagen / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism*; D005786:Gene Expression Regulation; D055786:Gene Knockout Techniques; D006487:Hemostasis; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D015539:Platelet Activation; D010973:Platelet Adhesiveness; D010974:Platelet Aggregation; D042787:Receptor, TIE-2 / Q000378:metabolism; D013927:Thrombosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology
chemical_list: C484196:Lrrc32 protein, mouse; D008565:Membrane Proteins; D003094:Collagen; D042787:Receptor, TIE-2; C079086:Tek protein, mouse