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Loss of receptor-mediated lipid uptake via scavenger receptor A or CD36 pathways does not ameliorate atherosclerosis in hyperlipidemic mice.
J Clin Invest. 2005 Aug; 115(8):2192-201.JCI

Abstract

Macrophage internalization of modified lipoproteins is thought to play a critical role in the initiation of atherogenesis. Two scavenger receptors, scavenger receptor A (SR-A) and CD36, have been centrally implicated in this lipid uptake process. Previous studies showed that these receptors mediated the majority of cholesterol ester accumulation in macrophages exposed to oxidized LDL and that mice with deletions of either receptor exhibited marked reductions in atherosclerosis. This work has contributed to an atherosclerosis paradigm: scavenger receptor-mediated oxidized lipoprotein uptake is required for foam cell formation and atherogenesis. In this study, Apoe-/- mice lacking SR-A or CD36, backcrossed into the C57BL/6 strain for 7 generations, were fed an atherogenic diet for 8 weeks. Hyperlipidemic Cd36-/-Apoe-/- and Msr1-/-Apoe-/- mice showed significant reductions in peritoneal macrophage lipid accumulation in vivo; however, in contrast with previous reports, this was associated with increased aortic sinus lesion areas. Characterization of aortic sinus lesions by electron microscopy and immunohistochemistry showed abundant macrophage foam cells, indicating that lipid uptake by intimal macrophages occurs in the absence of CD36 or SR-A. These data show that alternative lipid uptake mechanisms may contribute to macrophage cholesterol ester accumulation in vivo and suggest that the roles of SR-A and CD36 as proatherosclerotic mediators of modified LDL uptake in vivo need to be reassessed.

Authors+Show Affiliations

Lipid Metabolism Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA.No 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, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

16075060

Citation

Moore, Kathryn J., et al. "Loss of Receptor-mediated Lipid Uptake Via Scavenger Receptor a or CD36 Pathways Does Not Ameliorate Atherosclerosis in Hyperlipidemic Mice." The Journal of Clinical Investigation, vol. 115, no. 8, 2005, pp. 2192-201.
Moore KJ, Kunjathoor VV, Koehn SL, et al. Loss of receptor-mediated lipid uptake via scavenger receptor A or CD36 pathways does not ameliorate atherosclerosis in hyperlipidemic mice. J Clin Invest. 2005;115(8):2192-201.
Moore, K. J., Kunjathoor, V. V., Koehn, S. L., Manning, J. J., Tseng, A. A., Silver, J. M., McKee, M., & Freeman, M. W. (2005). Loss of receptor-mediated lipid uptake via scavenger receptor A or CD36 pathways does not ameliorate atherosclerosis in hyperlipidemic mice. The Journal of Clinical Investigation, 115(8), 2192-201.
Moore KJ, et al. Loss of Receptor-mediated Lipid Uptake Via Scavenger Receptor a or CD36 Pathways Does Not Ameliorate Atherosclerosis in Hyperlipidemic Mice. J Clin Invest. 2005;115(8):2192-201. PubMed PMID: 16075060.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Loss of receptor-mediated lipid uptake via scavenger receptor A or CD36 pathways does not ameliorate atherosclerosis in hyperlipidemic mice. AU - Moore,Kathryn J, AU - Kunjathoor,Vidya V, AU - Koehn,Stephanie L, AU - Manning,Jennifer J, AU - Tseng,Anita A, AU - Silver,Jessica M, AU - McKee,Mary, AU - Freeman,Mason W, PY - 2004/11/30/received PY - 2005/04/26/accepted PY - 2005/8/3/pubmed PY - 2005/10/12/medline PY - 2005/8/3/entrez SP - 2192 EP - 201 JF - The Journal of clinical investigation JO - J Clin Invest VL - 115 IS - 8 N2 - Macrophage internalization of modified lipoproteins is thought to play a critical role in the initiation of atherogenesis. Two scavenger receptors, scavenger receptor A (SR-A) and CD36, have been centrally implicated in this lipid uptake process. Previous studies showed that these receptors mediated the majority of cholesterol ester accumulation in macrophages exposed to oxidized LDL and that mice with deletions of either receptor exhibited marked reductions in atherosclerosis. This work has contributed to an atherosclerosis paradigm: scavenger receptor-mediated oxidized lipoprotein uptake is required for foam cell formation and atherogenesis. In this study, Apoe-/- mice lacking SR-A or CD36, backcrossed into the C57BL/6 strain for 7 generations, were fed an atherogenic diet for 8 weeks. Hyperlipidemic Cd36-/-Apoe-/- and Msr1-/-Apoe-/- mice showed significant reductions in peritoneal macrophage lipid accumulation in vivo; however, in contrast with previous reports, this was associated with increased aortic sinus lesion areas. Characterization of aortic sinus lesions by electron microscopy and immunohistochemistry showed abundant macrophage foam cells, indicating that lipid uptake by intimal macrophages occurs in the absence of CD36 or SR-A. These data show that alternative lipid uptake mechanisms may contribute to macrophage cholesterol ester accumulation in vivo and suggest that the roles of SR-A and CD36 as proatherosclerotic mediators of modified LDL uptake in vivo need to be reassessed. SN - 0021-9738 UR - https://www.unboundmedicine.com/medline/citation/16075060/Loss_of_receptor_mediated_lipid_uptake_via_scavenger_receptor_A_or_CD36_pathways_does_not_ameliorate_atherosclerosis_in_hyperlipidemic_mice_ L2 - https://doi.org/10.1172/JCI24061 DB - PRIME DP - Unbound Medicine ER -