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J. Biol. Chem., Vol. 283, Issue 16, 10408-10414, April 18, 2008

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

Mohammad Z. Ashraf, Niladri S. Kar, Xi Chen, Jaewoo Choi, Robert G. Salomon, Maria Febbraio^¶, and Eugene A. Podrez¹

From the Department of Molecular Cardiology and the ^¶Department of Cell Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195 and the Department of Chemistry, Case Western Reserve University, Cleveland, Ohio 44106

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.

Received for publication, December 23, 2007 , and in revised form, February 14, 2008.

^* This work was supported in part by National Institutes of Health Grants HL053315, HL077213 (to E. A. P.), HL53315 (to R. G. S.), and HL70083 (to M. F.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed: Cleveland Clinic, Lerner Research Institute, Dept. of Molecular Cardiology, ND-50, 9500 Euclid Ave., Cleveland, OH 44195. Tel.: 216-444-1019; Fax: 216-445-8204; E-mail: podreze{at}ccf.org.

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