Serum low density lipoprotein of alcoholic patients is chemically modified in vivo and induces apolipoprotein E synthesis by macrophages.
This work was carried out to investigate the effect of alcohol drinking on serum LDL. Agarose gel electrophoresis showed that LDL samples from alcoholic patients without serious liver disease were more negatively charged and moved faster toward the cathode than LDL from nondrinking control subjects. Rabbit antibodies raised by using keyhole limpet hemocyanin modified in vitro by 4-hydroxynonenal or by acetaldehyde as immunogens reacted more strongly with patients' LDL than with control LDL, indicating the presence of oxidatively modified epitopes and acetaldehyde adducts in alcoholic patients' LDL. LDL of alcoholic patients has decreased vitamin E contents. The electromobility of LDL decreased after abstinence from alcohol and returned to normal in 2 wk, but this was not accompanied by a significant increase in its vitamin E contents. When incubated with mouse peritoneal macrophages, patients' LDL induced apolipoprotein E secretion by threefold over control LDL with a concomitant increase in cellular cholesterol. Our results thus demonstrate that LDL of alcoholic patients has lower vitamin E content, is chemically modified in vivo, and exhibits altered biological function. These changes in heavy alcoholic drinkers may render LDL more atherogenic and thereby may counter the antiatherosclerosis effects of moderate alcohol consumption.
Lin
R C
RC
Department of Medicine, Indiana University School of Medicine, Indianapolis 46202, USA.
Dai
J
J
Lumeng
L
L
Zhang
M Y
MY
D000328:Adult; D000367:Age Factors; D000368:Aged; D000437:Alcoholism / Q000097:blood*; D000704:Analysis of Variance; D000818:Animals; D001057:Apolipoproteins E / Q000096:biosynthesis*; D001219:Aspartate Aminotransferases / Q000097:blood; D002784:Cholesterol / Q000097:blood; D004587:Electrophoresis, Agar Gel; D005260:Female; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood* / Q000302:isolation & purification / Q000494:pharmacology*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008875:Middle Aged; D010743:Phospholipids / Q000097:blood; D012016:Reference Values; D012044:Regression Analysis; D012727:Sex Characteristics; D013695:Temperance; D013997:Time Factors; D014280:Triglycerides / Q000097:blood; D014810:Vitamin E / Q000097:blood
D001057:Apolipoproteins E; D008077:Lipoproteins, LDL; D010743:Phospholipids; D014280:Triglycerides; D014810:Vitamin E; D002784:Cholesterol; D001219:Aspartate Aminotransferases