Effect of serum subfractions from peritoneal dialysis patients on Hep-G2 cell apolipoprotein A-I and B metabolism

Abstract

We previously showed that uremic serum subfractions isolated from hemodialysis (HD) patients inhibited the production of apolipoprotein (apo) A-I by human hepatoblastoma cells, Hep-G2. Because of the reported differences in atherogenic cardiovascular mortality between HD and peritoneal dialysis (PD) patients, we examined the effect of similar subfractions from PD patients on apo A-I and apo B synthesis. After obtaining informed consent, serum samples from five normal subjects and nine stable PD patients were applied to Sephadex G-25 columns to obtain the serum subfractions used in the various experiments. Sephadex G-25 chromatograms of PD sera showed a broad peak from fractions 30 through 60 (molecular wt 500 to 2000 Da). Control serum showed no peak in this region. PD serum subfractions decreased apo A-I synthesis, secretion, and apo A-I mRNA expression by Hep-G2 cells when compared to subfractions from control subjects. Cholesterol efflux studies showed that conditioned media obtained from Hep-G2 cells incubated with PD serum subfractions inhibited cholesterol efflux from fibroblasts, suggesting a biologically-significant decrease in apo A-I synthesis. PD serum subfractions increased protein synthesis and mRNA expression of apo B by Hep-G2 cells. Therefore, serum subfractions obtained from PD patients decreased apo A-I and increased apo B synthesis, findings consistent with their serum lipoprotein profiles suggesting that a biologically-active component in these subfractions could contribute to the risk of atherogenic cardiovascular disease in PD.