Suppression of Apoprotein-E Receptor by LP-X

Cholestasis brings about numerous changes in hepatic lipoprotein metabolism. The most pronounced alterations are hypercholesterolemia, hyperlipidemia and appearance of a unique lipoprotein, lipoprotein-X, in plasma. This lipoprotein is characterized by a high content of phospholipids and unesterified cholesterol with a small amount of protein. About 60% of the protein is albumin which is in the core of the vesicle. Apo-C forms the surface apoprotein, whereas apo-B and apo-E are absent. Lipoprotein-X is formed when bile lipids reflux into the plasma [1–4]. Even though LP-X is rich in cholesterol, it is surprising that cholesterol circulating in the form of LP-X does not exert feed-back control through HMG-CoA reducta-se on hepatic cholesterol synthesis during cholestasis. Despite the high cholesterol content of LP-X, its infusion has no significant effect on hepatic cholesterol biosynthesis in normal rats or in rats with a bile fistula [5], in contrast to the inhibitory effect of LDL. As a result of a disturbance in cholesterol homeostasis, hepatic cholesterol synthesis is increased in cholestasis [6]. Its role as a possible causative factor for cholestatic hypercholesterolemia has gained interest in recent years [7].