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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2000;20:2643.)
© 2000 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Involvement of Oxysterols and Lysophosphatidylcholine in the Oxidized LDL–Induced Impairment of Serum Albumin Synthesis by HEPG2 Cells

Presented in part at 5th Multiple Risk Factors in Cardiovascular Disease, Venice, Italy, October 1999.

Emmanuel Bourdon; Nadine Loreau; Jean Davignon; Lise Bernier; Denis Blache

From INSERM U498 (E.B., N.L., D.B.), Biochimie des Lipoprotéines et Interactions Vasculaires, Université de Bourgogne, Dijon, France, and the Hyperlipidemia and Atherosclerosis Research Group (J.D., L.B.), Clinical Research Institute of Montreal, Quebec, Canada.

Correspondence to Dr Denis Blache, INSERM U498, Biochimie des Lipoprotéines et Interactions Vasculaires, Faculté de Médecine, Université de Bourgogne, 7, Bd Jeanne d’Arc, 21033 Dijon, France. E-mail dblache{at}u-bourgogne.fr

Abstract—Oxidized low density lipoproteins (Ox-LDLs) are increasingly thought to be a key element in atherogenesis. We have previously reported that serum albumin has important antioxidant properties and that a reduced synthesis of albumin may represent a crucial point in the overall antioxidant defense. In the present work, we aimed at determining whether Ox-LDL could modulate albumin synthesis in cultured human hepatocytes (HepG2 cells). With the use of enzyme immunoassay and radiolabeled leucine incorporation followed by specific immunoprecipitation, Ox-LDL was found to lead to a dose-dependent decrease in albumin secretion. Moreover, the protein synthesis and mRNA levels were decreased in the presence of Ox-LDL, as assessed by Northern blot analysis. Because oxysterols and lysophospholipids are key components of Ox-LDL, we tested the effects of oxysterols (7-ketocholesterol and 25-hydroxycholesterol) and lysophosphatidylcholine on albumin secretion and expression. In our experimental conditions, we found that incubations with oxysterols or lysophosphatidylcholine at pathophysiological concentrations similar to those measured in Ox-LDLs reproduced the above-mentioned inhibitory effects on albumin synthesis. On the basis of our in vitro data, we propose that this newly described biological effect of Ox-LDL might partly explain the findings of epidemiological studies indicating that reduced levels of serum albumin are associated with increased mortality.

Key Words: oxidant stress • lipid peroxidation • liver • atherosclerosis