2. Academic Validation
  3. Platelet activation by oxidized low density lipoprotein is mediated by CD36 and scavenger receptor-A

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

  • Arterioscler Thromb Vasc Biol. 2007 Nov;27(11):2476-83. doi: 10.1161/ATVBAHA.107.150698.
Suzanne J A Korporaal 1,  Miranda Van Eck,  Jelle Adelmeijer,  Martin Ijsseldijk,  Ruud Out,  Ton Lisman,  Peter J Lenting,  Theo J C Van Berkel,  Jan-Willem N Akkerman
Affiliations

Affiliation

  • 1 Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, and Institute of Biomembranes, Utrecht University, The Netherlands.
PMID: 17761940 DOI: 10.1161/ATVBAHA.107.150698
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.

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.

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