title: Supporting roles of platelet thrombospondin-1 and CD36 in thrombus formation on collagen.
abstract: OBJECTIVE
  Platelets abundantly express the membrane receptor CD36 and store its ligand thrombospondin-1 (TSP1) in the α-granules. We investigated whether released TSP1 can support platelet adhesion and thrombus formation via interaction with CD36.
  
  
  RESULTS
  Mouse platelets deficient in CD36 showed reduced adhesion to TSP1 and subsequent phosphatidylserine expression. Deficiency in either CD36 or TSP1 resulted in markedly increased dissolution of thrombi formed on collagen, although thrombus buildup was unchanged. In mesenteric vessels in vivo, deficiency in CD36 prolonged the time to occlusion and enhanced embolization, which was in agreement with earlier observations in TSP1-deficient mice. Thrombi formed using wild-type blood stained positively for secreted TSP1. Releasate from wild-type but not from TSP1-deficient platelets enhanced platelet activation, phosphatidylserine expression, and thrombus formation on collagen. The enhancement was dependent on CD36 because it was without effect on thrombus formation by CD36-deficient platelets.
  
  
  CONCLUSIONS
  These results demonstrate an anchoring role of platelet-released TSP1 via CD36 in platelet adhesion and collagen-dependent thrombus stabilization. Thus, the TSP1-CD36 tandem is another platelet ligand-receptor axis contributing to the maintenance of a stable thrombus.
authors.affiliation: From the Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands (M.J.E.K., S.d.W., R.N.-U., R.v.K., J.M.E.M.C., J.W.M.H.); Department of Vascular Hematology/Angiogenesis (M.T.), Department of Metabolic Research (P.J.V.), and Department of Biopharmaceutics (S.J.A.K.), Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands; Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, The Netherlands (S.J.A.K.); Department of Dentistry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada (M.F.); Center for Molecular and Vascular Biology, Department of Cardiovascular Diseases, University of Leuven, Leuven, Belgium (P.V., M.F.H.); Laboratory of Vascular Hematology/Angiogenesis, Institute for Transfusion Medicine, DRK Blutspendedienst B-W-Hessen, Goethe University and University Hospital Frankfurt, Frankfurt, Germany (M.T.); and Metabolic Research Laboratories, University of Cambridge, Cambridge, United Kingdom (P.J.V.). Marijke.Kuijpers@maastrichtuniversity.nl.
authors.forename: Marijke J E
authors.initials: MJ
authors.lastname: Kuijpers
authors.affiliation: From the Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands (M.J.E.K., S.d.W., R.N.-U., R.v.K., J.M.E.M.C., J.W.M.H.); Department of Vascular Hematology/Angiogenesis (M.T.), Department of Metabolic Research (P.J.V.), and Department of Biopharmaceutics (S.J.A.K.), Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands; Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, The Netherlands (S.J.A.K.); Department of Dentistry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada (M.F.); Center for Molecular and Vascular Biology, Department of Cardiovascular Diseases, University of Leuven, Leuven, Belgium (P.V., M.F.H.); Laboratory of Vascular Hematology/Angiogenesis, Institute for Transfusion Medicine, DRK Blutspendedienst B-W-Hessen, Goethe University and University Hospital Frankfurt, Frankfurt, Germany (M.T.); and Metabolic Research Laboratories, University of Cambridge, Cambridge, United Kingdom (P.J.V.).
authors.forename: Susanne
authors.initials: S
authors.lastname: de Witt
authors.affiliation: From the Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands (M.J.E.K., S.d.W., R.N.-U., R.v.K., J.M.E.M.C., J.W.M.H.); Department of Vascular Hematology/Angiogenesis (M.T.), Department of Metabolic Research (P.J.V.), and Department of Biopharmaceutics (S.J.A.K.), Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands; Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, The Netherlands (S.J.A.K.); Department of Dentistry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada (M.F.); Center for Molecular and Vascular Biology, Department of Cardiovascular Diseases, University of Leuven, Leuven, Belgium (P.V., M.F.H.); Laboratory of Vascular Hematology/Angiogenesis, Institute for Transfusion Medicine, DRK Blutspendedienst B-W-Hessen, Goethe University and University Hospital Frankfurt, Frankfurt, Germany (M.T.); and Metabolic Research Laboratories, University of Cambridge, Cambridge, United Kingdom (P.J.V.).
authors.forename: Reyhan
authors.initials: R
authors.lastname: Nergiz-Unal
authors.affiliation: From the Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands (M.J.E.K., S.d.W., R.N.-U., R.v.K., J.M.E.M.C., J.W.M.H.); Department of Vascular Hematology/Angiogenesis (M.T.), Department of Metabolic Research (P.J.V.), and Department of Biopharmaceutics (S.J.A.K.), Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands; Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, The Netherlands (S.J.A.K.); Department of Dentistry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada (M.F.); Center for Molecular and Vascular Biology, Department of Cardiovascular Diseases, University of Leuven, Leuven, Belgium (P.V., M.F.H.); Laboratory of Vascular Hematology/Angiogenesis, Institute for Transfusion Medicine, DRK Blutspendedienst B-W-Hessen, Goethe University and University Hospital Frankfurt, Frankfurt, Germany (M.T.); and Metabolic Research Laboratories, University of Cambridge, Cambridge, United Kingdom (P.J.V.).
authors.forename: Roger
authors.initials: R
authors.lastname: van Kruchten
authors.affiliation: From the Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands (M.J.E.K., S.d.W., R.N.-U., R.v.K., J.M.E.M.C., J.W.M.H.); Department of Vascular Hematology/Angiogenesis (M.T.), Department of Metabolic Research (P.J.V.), and Department of Biopharmaceutics (S.J.A.K.), Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands; Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, The Netherlands (S.J.A.K.); Department of Dentistry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada (M.F.); Center for Molecular and Vascular Biology, Department of Cardiovascular Diseases, University of Leuven, Leuven, Belgium (P.V., M.F.H.); Laboratory of Vascular Hematology/Angiogenesis, Institute for Transfusion Medicine, DRK Blutspendedienst B-W-Hessen, Goethe University and University Hospital Frankfurt, Frankfurt, Germany (M.T.); and Metabolic Research Laboratories, University of Cambridge, Cambridge, United Kingdom (P.J.V.).
authors.forename: Suzanne J A
authors.initials: SJ
authors.lastname: Korporaal
authors.affiliation: From the Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands (M.J.E.K., S.d.W., R.N.-U., R.v.K., J.M.E.M.C., J.W.M.H.); Department of Vascular Hematology/Angiogenesis (M.T.), Department of Metabolic Research (P.J.V.), and Department of Biopharmaceutics (S.J.A.K.), Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands; Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, The Netherlands (S.J.A.K.); Department of Dentistry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada (M.F.); Center for Molecular and Vascular Biology, Department of Cardiovascular Diseases, University of Leuven, Leuven, Belgium (P.V., M.F.H.); Laboratory of Vascular Hematology/Angiogenesis, Institute for Transfusion Medicine, DRK Blutspendedienst B-W-Hessen, Goethe University and University Hospital Frankfurt, Frankfurt, Germany (M.T.); and Metabolic Research Laboratories, University of Cambridge, Cambridge, United Kingdom (P.J.V.).
authors.forename: Peter
authors.initials: P
authors.lastname: Verhamme
authors.affiliation: From the Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands (M.J.E.K., S.d.W., R.N.-U., R.v.K., J.M.E.M.C., J.W.M.H.); Department of Vascular Hematology/Angiogenesis (M.T.), Department of Metabolic Research (P.J.V.), and Department of Biopharmaceutics (S.J.A.K.), Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands; Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, The Netherlands (S.J.A.K.); Department of Dentistry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada (M.F.); Center for Molecular and Vascular Biology, Department of Cardiovascular Diseases, University of Leuven, Leuven, Belgium (P.V., M.F.H.); Laboratory of Vascular Hematology/Angiogenesis, Institute for Transfusion Medicine, DRK Blutspendedienst B-W-Hessen, Goethe University and University Hospital Frankfurt, Frankfurt, Germany (M.T.); and Metabolic Research Laboratories, University of Cambridge, Cambridge, United Kingdom (P.J.V.).
authors.forename: Maria
authors.initials: M
authors.lastname: Febbraio
authors.affiliation: From the Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands (M.J.E.K., S.d.W., R.N.-U., R.v.K., J.M.E.M.C., J.W.M.H.); Department of Vascular Hematology/Angiogenesis (M.T.), Department of Metabolic Research (P.J.V.), and Department of Biopharmaceutics (S.J.A.K.), Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands; Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, The Netherlands (S.J.A.K.); Department of Dentistry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada (M.F.); Center for Molecular and Vascular Biology, Department of Cardiovascular Diseases, University of Leuven, Leuven, Belgium (P.V., M.F.H.); Laboratory of Vascular Hematology/Angiogenesis, Institute for Transfusion Medicine, DRK Blutspendedienst B-W-Hessen, Goethe University and University Hospital Frankfurt, Frankfurt, Germany (M.T.); and Metabolic Research Laboratories, University of Cambridge, Cambridge, United Kingdom (P.J.V.).
authors.forename: Marc
authors.initials: M
authors.lastname: Tjwa
authors.affiliation: From the Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands (M.J.E.K., S.d.W., R.N.-U., R.v.K., J.M.E.M.C., J.W.M.H.); Department of Vascular Hematology/Angiogenesis (M.T.), Department of Metabolic Research (P.J.V.), and Department of Biopharmaceutics (S.J.A.K.), Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands; Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, The Netherlands (S.J.A.K.); Department of Dentistry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada (M.F.); Center for Molecular and Vascular Biology, Department of Cardiovascular Diseases, University of Leuven, Leuven, Belgium (P.V., M.F.H.); Laboratory of Vascular Hematology/Angiogenesis, Institute for Transfusion Medicine, DRK Blutspendedienst B-W-Hessen, Goethe University and University Hospital Frankfurt, Frankfurt, Germany (M.T.); and Metabolic Research Laboratories, University of Cambridge, Cambridge, United Kingdom (P.J.V.).
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Voshol
authors.affiliation: From the Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands (M.J.E.K., S.d.W., R.N.-U., R.v.K., J.M.E.M.C., J.W.M.H.); Department of Vascular Hematology/Angiogenesis (M.T.), Department of Metabolic Research (P.J.V.), and Department of Biopharmaceutics (S.J.A.K.), Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands; Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, The Netherlands (S.J.A.K.); Department of Dentistry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada (M.F.); Center for Molecular and Vascular Biology, Department of Cardiovascular Diseases, University of Leuven, Leuven, Belgium (P.V., M.F.H.); Laboratory of Vascular Hematology/Angiogenesis, Institute for Transfusion Medicine, DRK Blutspendedienst B-W-Hessen, Goethe University and University Hospital Frankfurt, Frankfurt, Germany (M.T.); and Metabolic Research Laboratories, University of Cambridge, Cambridge, United Kingdom (P.J.V.).
authors.forename: Marc F
authors.initials: MF
authors.lastname: Hoylaerts
authors.affiliation: From the Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands (M.J.E.K., S.d.W., R.N.-U., R.v.K., J.M.E.M.C., J.W.M.H.); Department of Vascular Hematology/Angiogenesis (M.T.), Department of Metabolic Research (P.J.V.), and Department of Biopharmaceutics (S.J.A.K.), Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands; Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, The Netherlands (S.J.A.K.); Department of Dentistry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada (M.F.); Center for Molecular and Vascular Biology, Department of Cardiovascular Diseases, University of Leuven, Leuven, Belgium (P.V., M.F.H.); Laboratory of Vascular Hematology/Angiogenesis, Institute for Transfusion Medicine, DRK Blutspendedienst B-W-Hessen, Goethe University and University Hospital Frankfurt, Frankfurt, Germany (M.T.); and Metabolic Research Laboratories, University of Cambridge, Cambridge, United Kingdom (P.J.V.).
authors.forename: Judith M E M
authors.initials: JM
authors.lastname: Cosemans
authors.affiliation: From the Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands (M.J.E.K., S.d.W., R.N.-U., R.v.K., J.M.E.M.C., J.W.M.H.); Department of Vascular Hematology/Angiogenesis (M.T.), Department of Metabolic Research (P.J.V.), and Department of Biopharmaceutics (S.J.A.K.), Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands; Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, The Netherlands (S.J.A.K.); Department of Dentistry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada (M.F.); Center for Molecular and Vascular Biology, Department of Cardiovascular Diseases, University of Leuven, Leuven, Belgium (P.V., M.F.H.); Laboratory of Vascular Hematology/Angiogenesis, Institute for Transfusion Medicine, DRK Blutspendedienst B-W-Hessen, Goethe University and University Hospital Frankfurt, Frankfurt, Germany (M.T.); and Metabolic Research Laboratories, University of Cambridge, Cambridge, United Kingdom (P.J.V.).
authors.forename: Johan W M
authors.initials: JW
authors.lastname: Heemskerk
mesh_terms: D000818:Animals; D018955:CD36 Antigens / Q000502:physiology*; D003094:Collagen / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D015539:Platelet Activation; D010973:Platelet Adhesiveness; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000502:physiology; D013927:Thrombosis / Q000209:etiology*; D019700:Thrombospondin 1 / Q000502:physiology*
chemical_list: D018955:CD36 Antigens; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D019700:Thrombospondin 1; D003094:Collagen
keywords: CD36; blood platelets; mice; thrombosis; thrombospondin 1