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Cholesterol Efflux to High-Density Lipoproteins and Apolipoprotein A-I Phosphatidylcholine Complexes Is Inhibited by Ethanol:  Role of Apolipoprotein Structure and Cooperative Interaction of Phosphatidylcholine and Cholesterol

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    Cholesterol Efflux to High-Density Lipoproteins and Apolipoprotein A-I Phosphatidylcholine Complexes Is Inhibited by Ethanol:  Role of Apolipoprotein Structure and Cooperative Interaction of Phosphatidylcholine and Cholesterol†
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    Geriatric Research, Education and Clinical Center, VA Medical Center, and Department of Pharmacology, University of Minnesota School of Medicine, Minneapolis, Minnesota 55417
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    Biochemistry

    Cite this: Biochemistry 2000, 39, 34, 10599–10606
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    https://doi.org/10.1021/bi0008534
    Published August 2, 2000
    Copyright © 2000 American Chemical Society
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    Abstract

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    There is a substantial body of evidence showing that moderate alcohol consumption is associated with a reduced risk of cardiovascular morbidity and mortality. One of the factors thought to contribute to this reduction in risk is an increase in the level of high-density lipoproteins (HDL) correlated with alcohol consumption. However, HDL levels are elevated in heavy drinkers, but their risk of vascular disease is greater compared with that of moderate drinkers. Ethanol at concentrations observed in heavy drinkers and alcoholics may directly act on HDL and apolipoproteins and in turn modify cholesterol efflux. In this paper, we show that ethanol significantly inhibited cholesterol efflux from fibroblasts to HDL and to apolipoprotein A-I (apoA-I) complexed with phosphatidylcholine (PC). Ethanol significantly inhibited binding of PC to apoA-I, inhibited incorporation of cholesterol only when apoA-I contained PC, and did not alter incorporation of cholesterol into HDL. ApoA-I structure was altered by ethanol as monitored by steady-state fluorescence polarization of tryptophan residues. The absence of ethanol effects on incorporation of cholesterol into HDL versus inhibition of cholesterol incorporation into the apoA-I−PC complex suggests that the effects of ethanol on cholesterol efflux mediated by HDL involve interaction with the cell surface and that efflux mediated by the apoA-I−PC complex is a combination of aqueous diffusion and contact with the cell surface. In addition, effects of ethanol on apoA-I suggest that pre-β-HDL or lipid-free apoA-I may be more perturbed by ethanol than mature HDL, and such effects may be pathophysiological with respect to the process of reverse cholesterol transport in heavy drinkers and alcoholics.

    Copyright © 2000 American Chemical Society

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    †

     This work was supported by grants from the National Institutes of Health (AA-10806) and the Department of Veterans Affairs.

    *

     To whom correspondence should be addressed:  VA Medical Center, GRECC 11G, One Veterans Drive, Minneapolis, MN 55417. Phone:  (612) 725-2051. Fax:  (612) 725-2084. E-mail:  Woodx002@tc. umn.edu.

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    14. Branko Jakovljevic, Katarina Paunovic, Goran Belojevic, Vesna Stojanov. Mechanisms of protective effects of moderate alcohol consumption on the cardiovascular system. Srpski arhiv za celokupno lekarstvo 2004, 132 (9-10) , 334-339. https://doi.org/10.2298/SARH0410334J
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    16. Minna L. Hannuksela, Marja K. Liisanantti, Markku J. Savolainen. Effect of Alcohol on Lipids and Lipoproteins in Relation to Atherosclerosis. Critical Reviews in Clinical Laboratory Sciences 2002, 39 (3) , 225-283. https://doi.org/10.1080/10408360290795529
    17. M.S. van der Gaag, A. van Tol, S.H.F. Vermunt, L.M. Scheek, G. Schaafsma, H.F.J. Hendriks. Alcohol consumption stimulates early steps in reverse cholesterol transport. Journal of Lipid Research 2001, 42 (12) , 2077-2083. https://doi.org/10.1016/S0022-2275(20)31537-6
    18. Shivendra D. Shukla, Grace Y. Sun, W. Gibson Wood, Markku J. Savolainen, Christer Alling, Jan B. Hoek. Ethanol and Lipid Metabolic Signaling. Alcoholism: Clinical and Experimental Research 2001, 25 (s1) https://doi.org/10.1111/j.1530-0277.2001.tb02370.x
    19. W. Gibson Wood, Nicolai A. Avdulov, Svetlana V. Chochina, Urule Igbavboa. Lipid carrier proteins and ethanol. Journal of Biomedical Science 2001, 8 (1) , 114-118. https://doi.org/10.1007/BF02255979
    20. Markku J. Savolainen, Christer Alling, Jan B. Hoek, Shivendra D. Shukla, Grace Y. Sun, W. Gibson Wood. . Alcoholism Clinical and Experimental Research 2001, 33S. https://doi.org/10.1097/00000374-200105051-00006
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    Biochemistry

    Cite this: Biochemistry 2000, 39, 34, 10599–10606
    Click to copy citationCitation copied!
    https://doi.org/10.1021/bi0008534
    Published August 2, 2000
    Copyright © 2000 American Chemical Society
    Request reuse permissions

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