Specific Oxidized Phospholipids Inhibit Scavenger Receptor BI-mediated Selective Uptake of Cholesteryl Esters

Abstract

We have recently demonstrated that specific oxidized phospholipids (oxPCCD36) accumulate at sites of oxidative stress in vivo such as within atherosclerotic lesions, hyperlipidemic plasma, and plasma with low high-density lipoprotein levels. oxPCCD36 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 oxPCCD36 represent ligands for another member of the scavenger receptor class B, type I (SR-BI). oxPCCD36 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, oxPCCD36 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.