| First Author | Korporaal SJ | Year | 2007 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 27 |
| Issue | 11 | Pages | 2476-83 |
| PubMed ID | 17761940 | Mgi Jnum | J:135004 |
| Mgi Id | MGI:3790245 | Doi | 10.1161/ATVBAHA.107.150698 |
| Citation | Korporaal SJ, et al. (2007) Platelet activation by oxidized low density lipoprotein is mediated by CD36 and scavenger receptor-A. Arterioscler Thromb Vasc Biol 27(11):2476-83 |
| abstractText | 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. METHODS AND 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%. CONCLUSION: These findings reveal a novel platelet-activating pathway stimulated by oxLDL that is initiated by the combined action of CD36 and SR-A. |
