Controversy over the atherogenicity of lipoprotein-X

Lipoprotein-X (Lp-X) is an abnormal lipoprotein containing abundant free cholesterol and phospholipids, as well as some apolipoprotein E (apoE). Serum Lp-X increases in patients with cholestasis and lecithin-cholesterol acyltransferase deficiency, as well as in those receiving intravenous lipid emulsion. Lp-X is often associated with skin xanthomas in cholestatic patients. However, earlier studies showed that Lp-X is not taken up by murine macrophages, but exerts antiatherogenic actions. In this review, we discuss the heterogeneity of Lp-X and its potential atherogenicity.

Mass spectrometry revealed that Lp-X of cholestatic patients is similar in lipid composition to low-density lipoprotein (LDL) and high-density lipoprotein, but not to bile acids, suggesting that Lp-X is synthesized in the liver. Palmar xanthomas appear in patients with cholestasis, but regress over months after improvement of hypercholesterolemia. Lp-X isolated from cholestatic patients is rich in apoE, and causes more lipid accumulation than oxidized LDL and acetyl LDL in human monocyte-derived macrophages.

Lp-X is heterogeneous in apoE content. Lp-X is taken up in cholestatic patients by apoE-recognizing lipoprotein receptors. Further research is warranted to fully understand the atherogenicity of Lp-X and the clinical significance of elevated Lp-X concentrations, particularly in cholestatic patients.