Serum low density lipoprotein of alcoholic patients is chemically modified in vivo and induces apolipoprotein E synthesis by macrophages.

Abstract

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. (J. Clin. Invest. 1995Invest. . 95:1979Invest. -1986

Induction of cytochrome P450 enzymes and generation of protein-aldehyde adducts are associated with sex-dependent sensitivity to alcohol-induced liver disease in micropigs

“…29 CYP2A may actually be a major catalyst of xenobiotic metabolism in damaged liver. 30 Taken together, the above data indicate a generalized induction of CYPs by ethanol, which may in turn be associated with a variety of adverse effects reported previously as a result of the generation of reactive aldehydes and enhanced oxidant stress, [31][32][33][34][35] including stimulation of fibrogenesis 36,37 and malignant transformation. 24 In light of previous studies indicating a greater susceptibility of women for alcohol-induced liver injury, 3,38,39 it should be noted that in the present experimental model serum testosterone and 17-␤-EST levels were associated with the amount of CYP enzymes, in particular with CYP2E1.…”

Oxidative Stress, Metabolism of Ethanol and Alcohol-Related Diseases

“…LDL of alcoholic patients has a lower vitamin E content, is chemically modified in vivo and exhibits altered biological functions. These changes in heavy alcoholics may make LDL more atherogenic and thereby may diminish the antiatherosclerotic effects of moderate alcohol consumption [45].…”

Changes in Serum Apolipoprotein and Lipoprotein Profile After Alcohol Withdrawal: Effect of Apolipoprotein E Polymorphism

“…Apos have been reported to form acetaldehyde adducts (Kervinen et al, 1995;Lin et al, 1995;Paradis et al, 1996), which may alter protein functions. The lower levels of all LDL components and the lower number of LDL particles in the alcohol abusers may be due to the formation of acetaldehyde adducts to apoB (Wehr et al, 1993); this may reduce the conversion of VLDL to LDL (Kervinen et al, 1995) and increase the clearance of LDL particles (Kesaniemi et al, 1987;Savolainen et al, 1987), thus leading to lower LDL levels whatever the apoE genotype.…”