Platelet activation by oxidized low density lipoprotein is mediated by CD36 and scavenger receptor-A.
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.
Korporaal
Suzanne J A
SJ
Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, and Institute of Biomembranes, Utrecht University, The Netherlands.
Van Eck
Miranda
M
Adelmeijer
Jelle
J
Ijsseldijk
Martin
M
Out
Ruud
R
Lisman
Ton
T
Lenting
Peter J
PJ
Van Berkel
Theo J C
TJ
Akkerman
Jan-Willem N
JW
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
D018955:CD36 Antigens; D008077:Lipoproteins, LDL; D051117:Scavenger Receptors, Class A; C099252:oxidized low density lipoprotein; D048051:p38 Mitogen-Activated Protein Kinases