UREMIC SERUM SUBFRACTION INHIBITS APOLIPOPROTEIN-A-I PRODUCTION BY A HUMAN HEPATOMA-CELL LINE

Abnormalities in lipoprotein metabolism are common in uremic patients and may represent an additional risk factor for the development of ath erosclerosis. Despite the frequent occurrence of lipoprotein abnormali ties, the role of various serum toxins and subfractions that accumulat e in uremic patients on lipoprotein metabolism is not clearly understo od. This study addressed the role of uremic toxins on lipoprotein meta bolism by examining the effect of a 500 to 2,000-d subfraction obtaine d from the serum of uremic and control subjects on the synthesis of ap olipoprotein (ape) A-1 in a human hepatoma cell line (Hep-G2). Serum s ubfractions obtained from uremic patients inhibited apo A-1 synthesis and secretion by Hep-G2 cells in a dose-dependent manner as measured b y (H-3)leucine incorporation into apo A-1, immunoprecipitation, and EL ISA. The uremic serum subfraction decreased the mRNA expression for ap o A-1 in Hep-G2 cells when compared with controls. These observations suggest that a component of uremic serum can have the potential to inh ibit hepatic apo A-1 synthesis and may adversely influence high-densit y lipoprotein metabolism, thus increasing the risk for the development of atherosclerotic vascular complications in uremic patients.