Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23:712-719
Published online before print January 23, 2003, doi: 10.1161/01.ATV.0000057572.97137.DD
Published online before print January 23, 2003, doi: 10.1161/01.ATV.0000057572.97137.DD
© 2003 American Heart Association, Inc.
ATVB In Focus |
Importance of Different Pathways of Cellular Cholesterol Efflux
From the Division of Gastroenterology and Nutrition, Department of Pediatrics, Children’s Hospital of Philadelphia, University of Pennsylvania School Medicine, Philadelphia, Pa.
Correspondence to Dr George Rothblat, Division of Gastroenterology and Nutrition, Department of Pediatrics, Abramson Research Center, Suite 302, Children’s Hospital of Philadelphia, University of Pennsylvania School of Medicine, 3615 Civic Center Blvd, Philadelphia, PA 19104-4318. E-mail rothblat{at}email.chop.edu
The removal of excess free cholesterol from cells by HDL or its apolipoproteins is important for maintaining cellular cholesterol homeostasis. This process is most likely compromised in the atherosclerotic lesion because the development of atherosclerosis is associated with low HDL cholesterol. Multiple mechanisms for efflux of cell cholesterol exist. Efflux of free cholesterol via aqueous diffusion occurs with all cell types but is inefficient. Efflux of cholesterol is accelerated when scavenger receptor class-B type I (SR-BI) is present in the cell plasma membrane. Both diffusion-mediated and SR-BI–mediated efflux occur to phospholipid-containing acceptors (ie, HDL and lipidated apolipoproteins); in both cases, the flux of cholesterol is bidirectional, with the direction of net flux depending on the cholesterol gradient. The ATP-binding cassette transporter AI (ABCA1) mediates efflux of both cellular cholesterol and phospholipid. In contrast to SR-BI–mediated flux, efflux via ABCA1 is unidirectional, occurring to lipid-poor apolipoproteins. The relative importance of the SR-BI and ABCA1 efflux pathways in preventing the development of atherosclerotic plaque is not known but will depend on the expression levels of the two proteins and on the type of cholesterol acceptors available.
Key Words: cholesterol efflux • scavenger receptor class-BI • ATP-binding cassette transporter AI • reverse cholesterol transport
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E. Favari, M. Lee, L. Calabresi, G. Franceschini, F. Zimetti, F. Bernini, and P. T. Kovanen Depletion of Pre-{beta}-high Density Lipoprotein by Human Chymase Impairs ATP-binding Cassette Transporter A1- but Not Scavenger Receptor Class B Type I-mediated Lipid Efflux to High Density Lipoprotein J. Biol. Chem., March 12, 2004; 279(11): 9930 - 9936. [Abstract] [Full Text] [PDF]
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H. B. Brewer Jr. High-Density Lipoproteins: A New Potential Therapeutic Target for the Prevention of Cardiovascular Disease Arterioscler Thromb Vasc Biol, March 1, 2004; 24(3): 387 - 391. [Full Text]
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K.-A. Rye and P. J. Barter Formation and Metabolism of Prebeta-Migrating, Lipid-Poor Apolipoprotein A-I Arterioscler Thromb Vasc Biol, March 1, 2004; 24(3): 421 - 428. [Abstract] [Full Text]
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G. Rossoni, M. Gomaraschi, F. Berti, C. R. Sirtori, G. Franceschini, and L. Calabresi Synthetic High-Density Lipoproteins Exert Cardioprotective Effects in Myocardial Ischemia/Reperfusion Injury J. Pharmacol. Exp. Ther., January 1, 2004; 308(1): 79 - 84. [Abstract] [Full Text] [PDF]
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N. Wang, D. Lan, M. Gerbod-Giannone, P. Linsel-Nitschke, A. W. Jehle, W. Chen, L. O. Martinez, and A. R. Tall ATP-binding Cassette Transporter A7 (ABCA7) Binds Apolipoprotein A-I and Mediates Cellular Phospholipid but Not Cholesterol Efflux J. Biol. Chem., October 31, 2003; 278(44): 42906 - 42912. [Abstract] [Full Text] [PDF]
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L. Liu, A. E. Bortnick, M. Nickel, P. Dhanasekaran, P. V. Subbaiah, S. Lund-Katz, G. H. Rothblat, and M. C. Phillips Effects of Apolipoprotein A-I on ATP-binding Cassette Transporter A1-mediated Efflux of Macrophage Phospholipid and Cholesterol: FORMATION OF NASCENT HIGH DENSITY LIPOPROTEIN PARTICLES J. Biol. Chem., October 31, 2003; 278(44): 42976 - 42984. [Abstract] [Full Text] [PDF]
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K. E. Schmid, W. S. Davidson, L. Myatt, and L. A. Woollett Transport of cholesterol across a BeWo cell monolayer: implications for net transport of sterol from maternal to fetal circulation J. Lipid Res., October 1, 2003; 44(10): 1909 - 1918. [Abstract] [Full Text] [PDF]
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O. L. Francone SR-BI: A New Player in an Old Game Arterioscler Thromb Vasc Biol, September 1, 2003; 23(9): 1486 - 1487. [Full Text] [PDF]
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A. R. Tall ATVB In Focus: Role of ABCA1 in Cellular Cholesterol Efflux and Reverse Cholesterol Transport Arterioscler Thromb Vasc Biol, May 1, 2003; 23(5): 710 - 711. [Full Text] [PDF]
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