Signaling role of CD36 in platelet activation and thrombus formation on immobilized thrombospondin or oxidized low-density lipoprotein

R. Nergiz-Unal, M. M. E. Lamers, R. Van Kruchten, J. J. Luiken, J. M. E. M. Cosemans, J. F. C. Glatz, M. J. E. Kuijpers, J. W. M. Heemskerk*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

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 Ca2+ rises, and resulted in exposure of P-selectin and integrin activation, all in a CD36-dependent manner with additional contributions of alpha(IIb)beta(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 alpha(IIb)beta(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 Ca2+ signaling mechanism, which enhances collagen-dependent thrombus formation under flow. These findings provide novel insight into the role of CD36 in hemostasis.
Original languageEnglish
Pages (from-to)1835-1846
JournalJournal of Thrombosis and Haemostasis
Volume9
Issue number9
DOIs
Publication statusPublished - Sep 2011

Keywords

  • CD36
  • outside-in signaling
  • oxidized low density lipoprotein
  • platelets
  • thrombospondin
  • thrombus

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