Marijke J E Kuijpers1, Susanne de Witt2, Reyhan Nergiz-Unal2, Roger van Kruchten2, Suzanne J A Korporaal2, Peter Verhamme2, Maria Febbraio2, Marc Tjwa2, Peter J Voshol2, Marc F Hoylaerts2, Judith M E M Cosemans2, Johan W M Heemskerk2. 1. 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. 2. 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.).
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. APPROACH AND 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.
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. APPROACH AND 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: Fernando Magdaleno; Elena Arriazu; Marina Ruiz de Galarreta; Yu Chen; Xiaodong Ge; Laura Conde de la Rosa; Natalia Nieto Journal: J Hepatol Date: 2016-06-15 Impact factor: 25.083
Authors: Katrin Herken; Martin Glauner; Stefanie C Robert; Matthias Maas; Sonja Zippel; Ulrike Nowak-Göttl; Barbara Zieger; Judith Lahav; Anke C Fender; Kerstin Jurk; Beate E Kehrel Journal: Int J Mol Sci Date: 2021-05-05 Impact factor: 5.923