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The Journal of Lipid Research, Vol. 40, 781-796, May 1999
Copyright © 1999 by Lipid Research, Inc.

Review

Cell cholesterol efflux: integration of old and new observations provides new insights

Correspondence to: George H. Rothblat

Numerous studies using a variety of cell/acceptor combinations have demonstrated differences in cholesterol efflux among cells. These studies also show that different acceptors, ranging from simple molecules like cyclodextrins to serum, stimulate efflux through a variety of mechanisms. By combining early observations with data derived from recent studies, it is now possible to formulate a model for cell cholesterol efflux which proposes that an array of different mechanisms, including aqueous diffusion, lipid-free apolipoprotein membrane microsolubilization, and SR-BI-mediated cholesterol exchange contribute to cholesterol flux. In this model the relative importance of each mechanism would be determined both by the cell type and the nature of the extracellular cholesterol acceptor.—Rothblat, G. H., M. de la Llera-Moya, V. Atger, G. Kellner-Weibel, D. L. Williams, and M. C. Phillips. Cell cholesterol efflux: integration of old and new observations provides new insights. J. Lipid Res. 1999. 40: 781–796.

Supplementary key words: tissue culture cells, cholesterol, efflux, influx, high density lipoprotein, lipoproteins, phospholipid, plasma membrane, cyclodextrin, scavenger receptor class B, type I, review

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				N. Fournier, A. Cogny, V. Atger, D. Pastier, D. Goudouneche, A. Nicoletti, N. Moatti, J. Chambaz, J.-L. Paul, and A.-D. Kalopissis Opposite Effects of Plasma From Human Apolipoprotein A-II Transgenic Mice on Cholesterol Efflux From J774 Macrophages and Fu5AH Hepatoma Cells Arterioscler. Thromb. Vasc. Biol., April 1, 2002; 22(4): 638 - 643. [Abstract] [Full Text] [PDF]

				K. Gillotte-Taylor, M. Nickel, W. J. Johnson, O. L. Francone, P. Holvoet, S. Lund-Katz, G. H. Rothblat, and M. C. Phillips Effects of Enrichment of Fibroblasts with Unesterified Cholesterol on the Efflux of Cellular Lipids to Apolipoprotein A-I J. Biol. Chem., March 29, 2002; 277(14): 11811 - 11820. [Abstract] [Full Text] [PDF]

				J. M. Baez, S. E. Barbour, and D. E. Cohen Phosphatidylcholine Transfer Protein Promotes Apolipoprotein A-I-mediated Lipid Efflux in Chinese Hamster Ovary Cells J. Biol. Chem., February 15, 2002; 277(8): 6198 - 6206. [Abstract] [Full Text] [PDF]

				S. Laitinen, M. Lehto, S. Lehtonen, K. Hyvarinen, S. Heino, E. Lehtonen, C. Ehnholm, E. Ikonen, and V. M. Olkkonen ORP2, a homolog of oxysterol binding protein, regulates cellular cholesterol metabolism J. Lipid Res., February 1, 2002; 43(2): 245 - 255. [Abstract] [Full Text] [PDF]

				D. Baldassarre, M. Amato, L. Pustina, E. Tremoli, C. R. Sirtori, L. Calabresi, and G. Franceschini Increased Carotid Artery Intima-Media Thickness in Subjects With Primary Hypoalphalipoproteinemia Arterioscler. Thromb. Vasc. Biol., February 1, 2002; 22(2): 317 - 322. [Abstract] [Full Text] [PDF]

				J. W. Chisholm, E. R. Burleson, G. S. Shelness, and J. S. Parks ApoA-I secretion from HepG2 cells: evidence for the secretion of both lipid-poor apoA-I and intracellularly assembled nascent HDL J. Lipid Res., January 1, 2002; 43(1): 36 - 44. [Abstract] [Full Text] [PDF]

				M. de la Llera-Moya, M. A. Connelly, D. Drazul, S. M. Klein, E. Favari, P. G. Yancey, D. L. Williams, and G. H. Rothblat Scavenger receptor class B type I affects cholesterol homeostasis by magnifying cholesterol flux between cells and HDL J. Lipid Res., December 1, 2001; 42(12): 1969 - 1978. [Abstract] [Full Text] [PDF]

				M. S. van der Gaag, A. van Tol, S. H. F. Vermunt, L. M. Scheek, G. Schaafsma, and H. F. J. Hendriks Alcohol consumption stimulates early steps in reverse cholesterol transport J. Lipid Res., December 1, 2001; 42(12): 2077 - 2083. [Abstract] [Full Text] [PDF]

				Z. H. Huang, C.-Y. Lin, J. F. Oram, and T. Mazzone Sterol Efflux Mediated by Endogenous Macrophage ApoE Expression Is Independent of ABCA1 Arterioscler. Thromb. Vasc. Biol., December 1, 2001; 21(12): 2019 - 2025. [Abstract] [Full Text] [PDF]

				G. Sowa, M. Pypaert, and W. C. Sessa Distinction between signaling mechanisms in lipid rafts vs. caveolae PNAS, November 9, 2001; (2001) 241409998. [Abstract] [Full Text] [PDF]

				P. K. Shah, S. Kaul, J. Nilsson, and B. Cercek Exploiting the Vascular Protective Effects of High-Density Lipoprotein and Its Apolipoproteins: An Idea Whose Time for Testing Is Coming, Part I Circulation, November 6, 2001; 104(19): 2376 - 2383. [Full Text] [PDF]

				F. Blanco-Vaca, J. C. Escola-Gil, J. M. Martin-Campos, and J. Julve Role of apoA-II in lipid metabolism and atherosclerosis: advances in the study of an enigmatic protein J. Lipid Res., November 1, 2001; 42(11): 1727 - 1739. [Abstract] [Full Text] [PDF]

				W. Khovidhunkit, A. H. Moser, J. K. Shigenaga, C. Grunfeld, and K. R. Feingold Regulation of scavenger receptor class B type I in hamster liver and Hep3B cells by endotoxin and cytokines J. Lipid Res., October 1, 2001; 42(10): 1636 - 1644. [Abstract] [Full Text] [PDF]

				J. F. Oram and R. M. Lawn ABCA1: the gatekeeper for eliminating excess tissue cholesterol J. Lipid Res., August 1, 2001; 42(8): 1173 - 1179. [Abstract] [Full Text] [PDF]

				W. Khovidhunkit, J. K. Shigenaga, A. H. Moser, K. R. Feingold, and C. Grunfeld Cholesterol efflux by acute-phase high density lipoprotein: role of lecithin:cholesterol acyltransferase J. Lipid Res., June 1, 2001; 42(6): 967 - 975. [Abstract] [Full Text]

				P. G. Frank, F. Galbiati, D. Volonte, B. Razani, D. E. Cohen, Y. L. Marcel, and M. P. Lisanti Influence of caveolin-1 on cellular cholesterol efflux mediated by high-density lipoproteins Am J Physiol Cell Physiol, May 1, 2001; 280(5): C1204 - C1214. [Abstract] [Full Text] [PDF]

				P. G. Yancey and W. G. Jerome Lysosomal cholesterol derived from mildly oxidized low density lipoprotein is resistant to efflux J. Lipid Res., March 1, 2001; 42(3): 317 - 327. [Abstract] [Full Text]

				B. Haidar, S. Mott, B. Boucher, C. Y. Lee, M. Marcil, and J. Genest , Jr. Cellular cholesterol efflux is modulated by phospholipid-derived signaling molecules in familial HDL deficiency/Tangier disease fibroblasts J. Lipid Res., February 1, 2001; 42(2): 249 - 257. [Abstract] [Full Text]

				A. von Eckardstein, J.-R. Nofer, and G. Assmann High Density Lipoproteins and Arteriosclerosis : Role of Cholesterol Efflux and Reverse Cholesterol Transport Arterioscler. Thromb. Vasc. Biol., January 1, 2001; 21(1): 13 - 27. [Abstract] [Full Text] [PDF]

				K. Simons and E. Ikonen How Cells Handle Cholesterol Science, December 1, 2000; 290(5497): 1721 - 1726. [Abstract] [Full Text]

				A. D. Tepper, P. Ruurs, T. Wiedmer, P. J. Sims, J. Borst, and W. J. van Blitterswijk Sphingomyelin Hydrolysis to Ceramide during the Execution Phase of Apoptosis Results from Phospholipid Scrambling and Alters Cell-surface Morphology J. Cell Biol., July 11, 2000; 150(1): 155 - 164. [Abstract] [Full Text] [PDF]

				J. A. M. Beentjes, A. van Tol, W. J. Sluiter, and R. P. F. Dullaart Effect of growth hormone replacement therapy on plasma lecithin:cholesterol acyltransferase and lipid transfer protein activities in growth hormone-deficient adults J. Lipid Res., June 1, 2000; 41(6): 925 - 932. [Abstract] [Full Text]

				A. R. Tall, X.-c. Jiang, Y. Luo, and D. Silver 1999 George Lyman Duff Memorial Lecture : Lipid Transfer Proteins, HDL Metabolism, and Atherogenesis Arterioscler. Thromb. Vasc. Biol., May 1, 2000; 20(5): 1185 - 1188. [Abstract] [Full Text] [PDF]

				N. Fournier, V. Atger, J.-L. Paul, M. Sturm, N. Duverger, G. H. Rothblat, and N. Moatti Human ApoA-IV Overexpression in Transgenic Mice Induces cAMP-Stimulated Cholesterol Efflux From J774 Macrophages to Whole Serum Arterioscler. Thromb. Vasc. Biol., May 1, 2000; 20(5): 1283 - 1292. [Abstract] [Full Text] [PDF]

				M. G. Sorci-Thomas, M. Thomas, L. Curtiss, and M. Landrum Single Repeat Deletion in ApoA-I Blocks Cholesterol Esterification and Results in Rapid Catabolism of Delta 6 and Wild-type ApoA-I in Transgenic Mice J. Biol. Chem., April 14, 2000; 275(16): 12156 - 12163. [Abstract] [Full Text] [PDF]

				J. McNeish, R. J. Aiello, D. Guyot, T. Turi, C. Gabel, C. Aldinger, K. L. Hoppe, M. L. Roach, L. J. Royer, J. de Wet, et al. High density lipoprotein deficiency and foam cell accumulation in mice with targeted disruption of ATP-binding cassette transporter-1 PNAS, April 11, 2000; 97(8): 4245 - 4250. [Abstract] [Full Text] [PDF]

				S Prattes, G Horl, A Hammer, A Blaschitz, W. Graier, W Sattler, R Zechner, and E Steyrer Intracellular distribution and mobilization of unesterified cholesterol in adipocytes: triglyceride droplets are surrounded by cholesterol-rich ER-like surface layer structures J. Cell Sci., January 9, 2000; 113(17): 2977 - 2989. [Abstract] [PDF]