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 and by oxidized LDL (oxLDL) through lysophosphatidic acid (LPA) signaling to Rho A and Ca. Here we report a new mechanism for platelet activation by oxLDL. METHODS AND RESULTS - Oxidation of nLDL increases p38 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 activation by oxLDL but combined blockade inhibits p38 by >40% and platelet adhesion to fibrinogen under flow by >60%. Mouse platelets deficient in either CD36 or SR-A show normal p38 activation by oxLDL but combined deficiency of CD36 and SR-A disrupts oxLDL-induced activation of p38 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. © 2007 American Heart Association, Inc.