Platelet activation by oxidized low density lipoprotein is mediated by CD36 and scavenger receptor-A

SJA Korporaal, M Van Eck, J Adelmeijer… - … , and vascular biology, 2007 - Am Heart Assoc
SJA Korporaal, M Van Eck, J Adelmeijer, M Ijsseldijk, R Out, T Lisman, PJ Lenting…
Arteriosclerosis, thrombosis, and vascular biology, 2007Am Heart Assoc
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 p38MAPK 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. Methods and Results—Oxidation
of nLDL increases p38MAPK activation through a mechanism that is (1) independent of LPA …
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 p38MAPK 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.
Methods and Results— Oxidation of nLDL increases p38MAPK 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 p38MAPK activation by oxLDL but combined blockade inhibits p38MAPK by >40% and platelet adhesion to fibrinogen under flow by >60%. Mouse platelets deficient in either CD36 or SR-A show normal p38MAPK activation by oxLDL but combined deficiency of CD36 and SR-A disrupts oxLDL-induced activation of p38MAPK by >70%.
Conclusion— These findings reveal a novel platelet-activating pathway stimulated by oxLDL that is initiated by the combined action of CD36 and SR-A.
Am Heart Assoc