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Signaling role of CD36 in platelet activation and thrombus formation on immobilized thrombospondin or oxidized low‐density lipoprotein
Author(s) -
NERGIZUNAL R.,
LAMERS M. M. E.,
VAN KRUCHTEN R.,
LUIKEN J. J.,
COSEMANS J. M. E. M.,
GLATZ J. F. C.,
KUIJPERS M. J. E.,
HEEMSKERK J. W. M.
Publication year - 2011
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/j.1538-7836.2011.04416.x
Subject(s) - cd36 , syk , platelet activation , platelet , thrombospondin , gpvi , chemistry , microbiology and biotechnology , thrombus , phosphatidylserine , platelet adhesiveness , platelet membrane glycoprotein , thrombospondin 1 , signal transduction , biochemistry , cancer research , medicine , tyrosine kinase , receptor , immunology , biology , angiogenesis , phospholipid , metalloproteinase , enzyme , platelet aggregation , membrane
Summary. Background and Objective: Platelets abundantly express glycoprotein CD36 with thrombospondin‐1 (TSP1) and oxidized low‐density lipoprotein (oxLDL) as proposed ligands. How these agents promote platelet activation is still poorly understood. Methods and Results: Both TSP1 and oxLDL caused limited activation of platelets in suspension. However, immobilized TSP1 and oxLDL, but not LDL, strongly supported platelet adhesion and spreading with a major role of CD36. Platelet spreading was accompanied by potent Ca 2+ rises, and resulted in exposure of P‐selectin and integrin activation, all in a CD36‐dependent manner with additional contributions of α IIb β 3 and ADP receptor stimulation. Signaling responses via CD36 involved activation of the protein tyrosine kinase Syk. In whole blood perfusion, co‐coating of TSP1 or oxLDL with collagen enhanced thrombus formation at high‐shear flow conditions, with increased expression on platelets of activated α IIb β 3 , P‐selectin and phosphatidylserine, again in a CD36‐dependent way. Conclusions: Immobilized TSP1 and oxLDL activate platelets partly via CD36 through a Syk kinase‐dependent Ca 2+ signaling mechanism, which enhances collagen‐dependent thrombus formation under flow. These findings provide novel insight into the role of CD36 in hemostasis.