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A novel family of atherogenic oxidized phospholipids promotes macrophage foam cell formation via the scavenger receptor CD36 and is enriched in atherosclerotic lesions.
J Biol Chem. 2002 Oct 11; 277(41):38517-23.JB

Abstract

The macrophage scavenger receptor CD36 plays an important role in binding and uptake of oxidized forms of low-density lipoprotein (LDL), foam cell formation, and lesion development during atherosclerosis. The structural basis of CD36-lipoprotein ligand recognition is an area of intense interest. In a companion article we reported the characterization of a structurally conserved family of oxidized choline glycerophospholipids (oxPC(CD36)) that serve as novel high affinity ligands for cells stably transfected with CD36, mediating recognition of multiple oxidized forms of LDL (Podrez, E. A., Poliakov, E., Shen, Z., Zhang, R., Deng, Y., Sun, M., Finton, P., Shan, L., Gugiu, B., Fox, P. L., Hoff, H. F., Salomon, R. G., and Hazen, S. L. (July 8, 2002) J. Biol. Chem. 277, 10.1074/jbc.M203318200). Here we use macrophages from wild-type and CD36 null mice to demonstrate that CD36 is the major receptor on macrophages mediating recognition of oxPC(CD36) species when presented (+/- plasma) in pure form, within PC bilayers in small unilamellar vesicles, and within liposomes generated from lipid extracts of native LDL. We also show that oxPC(CD36) promote CD36-dependent recognition when present at only a few molecules per particle, resulting in macrophage binding, uptake, metabolism, cholesterol accumulation, and foam cell formation. Finally, using high performance liquid chromatography with on-line electrospray ionization tandem mass spectrometry (LC/ESI/MS/MS), we demonstrate that oxPC(CD36) are generated in vivo and are enriched in atherosclerotic lesions. Collectively, our data suggest that formation of this novel family of oxidized phospholipids participates in CD36-mediated recognition of oxidized lipoproteins and foam cell formation in vivo.

Authors+Show Affiliations

Department of Cell Biology, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

12145296

Citation

Podrez, Eugene A., et al. "A Novel Family of Atherogenic Oxidized Phospholipids Promotes Macrophage Foam Cell Formation Via the Scavenger Receptor CD36 and Is Enriched in Atherosclerotic Lesions." The Journal of Biological Chemistry, vol. 277, no. 41, 2002, pp. 38517-23.
Podrez EA, Poliakov E, Shen Z, et al. A novel family of atherogenic oxidized phospholipids promotes macrophage foam cell formation via the scavenger receptor CD36 and is enriched in atherosclerotic lesions. J Biol Chem. 2002;277(41):38517-23.
Podrez, E. A., Poliakov, E., Shen, Z., Zhang, R., Deng, Y., Sun, M., Finton, P. J., Shan, L., Febbraio, M., Hajjar, D. P., Silverstein, R. L., Hoff, H. F., Salomon, R. G., & Hazen, S. L. (2002). A novel family of atherogenic oxidized phospholipids promotes macrophage foam cell formation via the scavenger receptor CD36 and is enriched in atherosclerotic lesions. The Journal of Biological Chemistry, 277(41), 38517-23.
Podrez EA, et al. A Novel Family of Atherogenic Oxidized Phospholipids Promotes Macrophage Foam Cell Formation Via the Scavenger Receptor CD36 and Is Enriched in Atherosclerotic Lesions. J Biol Chem. 2002 Oct 11;277(41):38517-23. PubMed PMID: 12145296.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A novel family of atherogenic oxidized phospholipids promotes macrophage foam cell formation via the scavenger receptor CD36 and is enriched in atherosclerotic lesions. AU - Podrez,Eugene A, AU - Poliakov,Eugenia, AU - Shen,Zhongzhou, AU - Zhang,Renliang, AU - Deng,Yijun, AU - Sun,Mingjiang, AU - Finton,Paula J, AU - Shan,Lian, AU - Febbraio,Maria, AU - Hajjar,David P, AU - Silverstein,Roy L, AU - Hoff,Henry F, AU - Salomon,Robert G, AU - Hazen,Stanley L, Y1 - 2002/07/26/ PY - 2002/7/30/pubmed PY - 2002/11/26/medline PY - 2002/7/30/entrez SP - 38517 EP - 23 JF - The Journal of biological chemistry JO - J Biol Chem VL - 277 IS - 41 N2 - The macrophage scavenger receptor CD36 plays an important role in binding and uptake of oxidized forms of low-density lipoprotein (LDL), foam cell formation, and lesion development during atherosclerosis. The structural basis of CD36-lipoprotein ligand recognition is an area of intense interest. In a companion article we reported the characterization of a structurally conserved family of oxidized choline glycerophospholipids (oxPC(CD36)) that serve as novel high affinity ligands for cells stably transfected with CD36, mediating recognition of multiple oxidized forms of LDL (Podrez, E. A., Poliakov, E., Shen, Z., Zhang, R., Deng, Y., Sun, M., Finton, P., Shan, L., Gugiu, B., Fox, P. L., Hoff, H. F., Salomon, R. G., and Hazen, S. L. (July 8, 2002) J. Biol. Chem. 277, 10.1074/jbc.M203318200). Here we use macrophages from wild-type and CD36 null mice to demonstrate that CD36 is the major receptor on macrophages mediating recognition of oxPC(CD36) species when presented (+/- plasma) in pure form, within PC bilayers in small unilamellar vesicles, and within liposomes generated from lipid extracts of native LDL. We also show that oxPC(CD36) promote CD36-dependent recognition when present at only a few molecules per particle, resulting in macrophage binding, uptake, metabolism, cholesterol accumulation, and foam cell formation. Finally, using high performance liquid chromatography with on-line electrospray ionization tandem mass spectrometry (LC/ESI/MS/MS), we demonstrate that oxPC(CD36) are generated in vivo and are enriched in atherosclerotic lesions. Collectively, our data suggest that formation of this novel family of oxidized phospholipids participates in CD36-mediated recognition of oxidized lipoproteins and foam cell formation in vivo. SN - 0021-9258 UR - https://www.unboundmedicine.com/medline/citation/12145296/A_novel_family_of_atherogenic_oxidized_phospholipids_promotes_macrophage_foam_cell_formation_via_the_scavenger_receptor_CD36_and_is_enriched_in_atherosclerotic_lesions_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0021-9258(18)36334-8 DB - PRIME DP - Unbound Medicine ER -