Platelet CD36 links hyperlipidemia, oxidant stress and a prothrombotic phenotype.
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.
Podrez
Eugene A
EA
Department of Molecular Cardiology, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA. podreze@ccf.org
Byzova
Tatiana V
TV
Febbraio
Maria
M
Salomon
Robert G
RG
Ma
Yi
Y
Valiyaveettil
Manojkumar
M
Poliakov
Eugenia
E
Sun
Mingjiang
M
Finton
Paula J
PJ
Curtis
Brian R
BR
Chen
Juhua
J
Zhang
Renliang
R
Silverstein
Roy L
RL
Hazen
Stanley L
SL
D000818:Animals; D015703:Antigens, CD / Q000502:physiology; D001792:Blood Platelets / Q000502:physiology*; D018955:CD36 Antigens / Q000235:genetics / Q000502:physiology*; D050171:Dyslipidemias / Q000097:blood / Q000235:genetics; D017353:Gene Deletion; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood* / Q000276:immunology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018384:Oxidative Stress; D010641:Phenotype; D010743:Phospholipids / Q000097:blood; D015539:Platelet Activation; D011516:Prothrombin / Q000235:genetics*; D013927:Thrombosis / Q000097:blood / Q000276:immunology*
D015703:Antigens, CD; D018955:CD36 Antigens; D010743:Phospholipids; D011516:Prothrombin