title: Signaling role of CD36 in platelet activation and thrombus formation on immobilized thrombospondin or oxidized low-density lipoprotein.
abstract: 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.
  
  
  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.
authors.affiliation: Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Nergiz-Unal
authors.forename: M M E
authors.initials: MM
authors.lastname: Lamers
authors.forename: R
authors.initials: R
authors.lastname: Van Kruchten
authors.forename: J J
authors.initials: JJ
authors.lastname: Luiken
authors.forename: J M E M
authors.initials: JM
authors.lastname: Cosemans
authors.forename: J F C
authors.initials: JF
authors.lastname: Glatz
authors.forename: M J E
authors.initials: MJ
authors.lastname: Kuijpers
authors.forename: J W M
authors.initials: JW
authors.lastname: Heemskerk
mesh_terms: D018955:CD36 Antigens / Q000097:blood*; D020013:Calcium Signaling; D002465:Cell Movement; D003094:Collagen / Q000494:pharmacology; D006801:Humans; D055767:Immobilized Proteins; D066298:In Vitro Techniques; D008077:Lipoproteins, LDL / Q000097:blood*; D018715:Microscopy, Video; D008954:Models, Biological; D015539:Platelet Activation / Q000187:drug effects / Q000502:physiology*; D010973:Platelet Adhesiveness; D015398:Signal Transduction; D013927:Thrombosis / Q000097:blood* / Q000209:etiology / Q000276:immunology*; D019700:Thrombospondin 1 / Q000097:blood*
chemical_list: D018955:CD36 Antigens; D055767:Immobilized Proteins; D008077:Lipoproteins, LDL; D019700:Thrombospondin 1; C099252:oxidized low density lipoprotein; D003094:Collagen