title: Platelet activation by oxidized low density lipoprotein is mediated by CD36 and scavenger receptor-A.
abstract: OBJECTIVE
  The interaction of platelets with low density lipoprotein (LDL) contributes to the development of cardiovascular disease. Platelets are activated by native LDL (nLDL) through apoE Receptor 2' (apoER2')-mediated signaling to p38(MAPK) and by oxidized LDL (oxLDL) through lysophosphatidic acid (LPA) signaling to Rho A and Ca2+. Here we report a new mechanism for platelet activation by oxLDL.
  
  
  RESULTS
  Oxidation of nLDL increases p38(MAPK) activation through a mechanism that is (1) independent of LPA, and (2) unlike nLDL-signaling not desensitized by prolonged platelet-LDL contact or inhibited by receptor-associated protein or chondroitinase ABC. Antibodies against scavenger receptors CD36 and SR-A alone fail to block p38(MAPK) activation by oxLDL but combined blockade inhibits p38(MAPK) by >40% and platelet adhesion to fibrinogen under flow by >60%. Mouse platelets deficient in either CD36 or SR-A show normal p38(MAPK) activation by oxLDL but combined deficiency of CD36 and SR-A disrupts oxLDL-induced activation of p38(MAPK) by >70%.
  
  
  CONCLUSIONS
  These findings reveal a novel platelet-activating pathway stimulated by oxLDL that is initiated by the combined action of CD36 and SR-A.
authors.affiliation: Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, and Institute of Biomembranes, Utrecht University, The Netherlands.
authors.forename: Suzanne J A
authors.initials: SJ
authors.lastname: Korporaal
authors.forename: Miranda
authors.initials: M
authors.lastname: Van Eck
authors.forename: Jelle
authors.initials: J
authors.lastname: Adelmeijer
authors.forename: Martin
authors.initials: M
authors.lastname: Ijsseldijk
authors.forename: Ruud
authors.initials: R
authors.lastname: Out
authors.forename: Ton
authors.initials: T
authors.lastname: Lisman
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Lenting
authors.forename: Theo J C
authors.initials: TJ
authors.lastname: Van Berkel
authors.forename: Jan-Willem N
authors.initials: JW
authors.lastname: Akkerman
mesh_terms: D000818:Animals; D001792:Blood Platelets; D018955:CD36 Antigens / Q000502:physiology*; D006801:Humans; D008077:Lipoproteins, LDL / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D015539:Platelet Activation / Q000502:physiology*; D051117:Scavenger Receptors, Class A / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D018955:CD36 Antigens; D008077:Lipoproteins, LDL; D051117:Scavenger Receptors, Class A; C099252:oxidized low density lipoprotein; D048051:p38 Mitogen-Activated Protein Kinases