Specific oxidized phospholipids inhibit scavenger receptor bi-mediated selective uptake of cholesteryl esters.
We have recently demonstrated that specific oxidized phospholipids (oxPC(CD36)) accumulate at sites of oxidative stress in vivo such as within atherosclerotic lesions, hyperlipidemic plasma, and plasma with low high-density lipoprotein levels. oxPC(CD36) serve as high affinity ligands for the scavenger receptor CD36, mediate uptake of oxidized low density lipoprotein by macrophages, and promote a pro-thrombotic state via platelet scavenger receptor CD36. We now report that oxPC(CD36) represent ligands for another member of the scavenger receptor class B, type I (SR-BI). oxPC(CD36) prevent binding to SR-BI of its physiological ligand, high density lipoprotein, because of the close proximity of the binding sites for these two ligands on SR-BI. Furthermore, oxPC(CD36) interfere with SR-BI-mediated selective uptake of cholesteryl esters in hepatocytes. Thus, oxidative stress and accumulation of specific oxidized phospholipids in plasma may have an inhibitory effect on reverse cholesterol transport.
Ashraf
Mohammad Z
MZ
Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA.
Kar
Niladri S
NS
Chen
Xi
X
Choi
Jaewoo
J
Salomon
Robert G
RG
Febbraio
Maria
M
Podrez
Eugene A
EA
D001692:Biological Transport; D018955:CD36 Antigens / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism; D002788:Cholesterol Esters / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D008954:Models, Biological; D018384:Oxidative Stress; D010743:Phospholipids / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D051116:Receptors, Scavenger / Q000378:metabolism*; D051122:Scavenger Receptors, Class B / Q000378:metabolism*
D018955:CD36 Antigens; D002788:Cholesterol Esters; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D010743:Phospholipids; D051116:Receptors, Scavenger; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B; D002784:Cholesterol