EFFECT OF SERUM SUBFRACTIONS FROM PERITONEAL-DIALYSIS PATIENTS ON HEP-G2 CELL APOLIPOPROTEIN-A-I AND APOLIPOPROTEIN-B METABOLISM

We previously showed that uremic serum subfractions isolated from hemo dialysis (HD) patients inhibited the production of apolipoprotein (apo ) A-I by human hepatoblastoma cells, Hep-G2. Because of the reported d ifferences in atherogenic cardiovascular mortality between HD and peri toneal dialysis (PD) patients, we examined the effect of similar subfr actions from PD patients on apo A-I and apo B synthesis. After obtaini ng 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 chr omatograms 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 r egion. PD serum subfractions decreased apo A-I synthesis, secretion, a nd apo A-I mRNA expression by Hep-G2 cells when compared to subfractio ns from control subjects. Cholesterol efflux studies showed that condi tioned media obtained from Hep-G2 cells incubated with PD serum subfra ctions inhibited cholesterol efflux from fibroblasts, suggesting a bio logically-significant decrease in apo A-I synthesis. PD serum subfract ions increased protein synthesis and mRNA expression of apo B by Hep-G 2 cells. Therefore, serum subfractions obtained from PD patients decre ased apo A-I and increased apo B synthesis, findings consistent with t heir serum lipoprotein profiles suggesting that a biologically-active component in these subfractions could contribute to the risk of athero genic cardiovascular disease in PD.