Involvement of oxysterols and lysophosphatidylcholine in the oxidized LDL-induced impairment of serum albumin synthesis by HEPG2 cells

Oxidized low density lipoproteins (Ox-LDLs) are increasingly thought to be a key element in atherogenesis. We have previously reported that serum albu min has important antioxidant properties and that a reduced synthesis of al bumin may represent a crucial point in the overall antioxidant defense. In the present work: we aimed at determining whether Ox-LDL could modulate alb umin synthesis in cultured human hepatocytes (HepG2 cells). With the use of enzyme immunoassay and radiolabeled leucine incorporation followed by spec ific immunoprecipitation, Ox-LDL was found to lead to a dose-dependent decr ease in albumin secretion. Moreover, the protein synthesis and mRNA levels were decreased in the presence of Ox-LDL, as assessed by Northern blot anal ysis. Because oxysterols and lysophospholipids are key components of Ox-LDL , we tested the effects of oxysterols (7-ketocholesterol and 25-hydroxychol esterol) and lysophosphatidylcholine on albumin secretion and expression. I n our experimental conditions, we found that incubation's with oxysterols o r lysophosphatidylcholine at pathophysiological concentrations similar to t hose measured in Ox-LDLs reproduced the above-mentioned inhibitory effects on albumin synthesis. On the basis of our in vitro data, we propose that th is newly described biological effect of Ox-LDL might partly explain the fin dings of epidemiological studies indicating that reduced levels of serum al bumin are associated with increased mortality.