Hypoalbuminemia increases lysophosphatidylcholine in low-density lipoprotein of normocholesterolemic subjects

Background. A phospholipid, lysophosphatidylcholine (LPC), is the major det erminant of the atherosclerotic properties of oxidized low-density lipoprot ein (LDL). Under normal circumstances most LPC is bound to albumin. We hypo thesized that lipoprotein LPC concentrations are increased in hypoalbuminem ic patients with the nephrotic syndrome, irrespective of their lipid levels . To test this hypothesis, we selected nephrotic and control subjects with matched LDL cholesterol levels. Methods. Lipoproteins and the albumin-rich lipoprotein-deficient fractions were separated by ultracentrifugation and their phospholipid composition wa s analyzed by thin-layer chromatography. Results. Nephrotic subjects (albumin 23 +/- 2 g/liter and LDL cholesterol 3 .1 +/- 0.2 mmol/liter) had a LDL LPC concentration that was increased (P < 0.05) to 66 +/- 7 vs. 35 +/- 6 mu mol/liter in matched controls (albumin 42 +/- 5 g/liter and LDL cholesterol 3.1 +/- 0.2 mmol/liter). LPC in very low -density lipoprotein plus intermediate-density lipoprotein (VLDL + IDL) in these subjects was also increased to 33 +/- 7 vs. 9 +/- 2 mu mol/liter in c ontrols (P < 0.05). Conversely, LPC was decreased to 19 +/- 4 mu mol/liter in the albumin-containing fraction of these hypoalbuminemic patients, as co mpared to 46 +/- 10 mu mol/liter in the controls (P < 0.05). LPC was also l ow (14 +/- 4 mu mol/liter) in the albumin-containing fraction of hypoalbumi nemic, hypocholesterolemic patients with nonrenal diseases. In hyperlipidem ic nephrotic subjects (albumin 21 +/- 2 g/liter and LDL cholesterol 5.7 +/- 0.5 mmol/liter) the LPC levels in LDL and VLDL + IDL were further increase d, to 95 +/- 20 and 56 +/- 23 mu mol/liter, respectively (P < 0.05). Conclusion. These findings suggest that in the presence of hypoalbuminemia in combination with proteinuria, LPC shifts from albumin to VLDL, IDL and L DL. This effect is independent of hyperlipidemia. Increased LPC in lipoprot eins may be an important factor in the disproportionate increase in cardiov ascular disease in nephrotic patients with hypoalbuminemia.