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Effects of chronic alcohol treatment on the synthesis, sialylation, and disposition of nascent apolipoprotein E by peritoneal macrophages of rats^1,2,3

¹ From the Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore; the Department of Medicine, George Washington University Medical Center, Washington, DC; and the Department of Veterans Affairs Medical Center, Washington, DC.

Background: Plasma apolipoprotein (apo) E, a sialoprotein, plays an important role in reverse cholesterol transport. Previously, we showed that chronic alcohol consumption impairs glycosylation of apo E in rat liver. Peritoneal macrophages are another significant apo E synthesis site.

Objective: The main purpose of this study was to determine the effects of chronic alcohol feeding of rats on the synthesis, sialylation, and sialic acid content of macrophage apo E and its ability to bind to the HDL₃ molecule in vitro.

Design: Rats were fed an alcoholic diet or an isoenergetic control diet for 8 wk, after which peritoneal macrophages isolated from them were cultured and analyzed for apo E metabolism.

Results: Macrophages from alcohol-fed rats accumulated 33.3% more (P < 0.05) cholesterol than did those from control rats when incubated with acetylated LDL. These macrophages showed a 51–57% lower relative sialylation rate of apo E (P < 0.001) but no significant difference in relative protein synthetic rate. The sialic acid content of the intracellular and secreted forms of apo E was reduced by 41.8% (P < 0.001) and 50.3% (P < 0.001), respectively, with chronic alcohol treatment. Secretion of newly synthesized apo E was impaired by 53.7% (P < 0.001) and 26.1% (P < 0.001) in the absence and presence of HDL in the medium, respectively. Macrophages of alcohol-treated rats secreted apo E with 47.6–67.2% lower (P < 0.001) HDL₃ binding ability; binding ability was restored completely by resialylation of the desialylated apo E.

Conclusion: In rats, an alcohol-mediated decrease in sialylation rate resulting in loss of sialic acid residues in apo E impairs the ability of apo E to bind to HDL and consequently in defective reverse cholesterol transport.

Key Words: Chronic ethanol feeding • macrophages • apolipoprotein E • glycosylation • sialylation • sialic acid content • high-density lipoproteins • HDL • reverse cholesterol transport • binding • atherosclerosis • rats • alcohol • coronary heart disease

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