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Nat Med. 2007 Sep;13(9):1086-95. Epub 2007 Aug 26.

Platelet CD36 links hyperlipidemia, oxidant stress and a prothrombotic phenotype.

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1
Department of Molecular Cardiology, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA. podreze@ccf.org

Abstract

Dyslipidemia is associated with a prothrombotic phenotype; however, the mechanisms responsible for enhanced platelet reactivity remain unclear. Proatherosclerotic lipid abnormalities are associated with both enhanced oxidant stress and the generation of biologically active oxidized lipids, including potential ligands for the scavenger receptor CD36, a major platelet glycoprotein. Using multiple mouse in vivo thrombosis models, we now demonstrate that genetic deletion of Cd36 protects mice from hyperlipidemia-associated enhanced platelet reactivity and the accompanying prothrombotic phenotype. Structurally defined oxidized choline glycerophospholipids that serve as high-affinity ligands for CD36 were at markedly increased levels in the plasma of hyperlipidemic mice and in the plasma of humans with low HDL levels, were able to bind platelets via CD36 and, at pathophysiological levels, promoted platelet activation via CD36. Thus, interactions of platelet CD36 with specific endogenous oxidized lipids play a crucial role in the well-known clinical associations between dyslipidemia, oxidant stress and a prothrombotic phenotype.

PMID:
17721545
PMCID:
PMC3042888
DOI:
10.1038/nm1626
[Indexed for MEDLINE]
Free PMC Article

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