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 drinkin g on serum LDL. Agarose gel electrophoresis showed that LDL samples fr om alcoholic patients without serious liver disease were more negative ly charged and moved faster toward the cathode than LDL from nondrinki ng 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 ace taldehyde adducts in alcoholic patients' LDL. LDL of alcoholic patient s has decreased vitamin E contents. The electromobility of LDL decreas ed after abstinence from alcohol and returned to normal in 2 wk, but t his was not accompanied by a significant increase in its vitamin E con tents. 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 demo nstrate 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 athero genic and thereby may counter the antiatherosclerosis effects of moder ate alcohol consumption.