Characterization of lipoproteins during human cholestasis

We have characterized changes in lipoproteins from cholestatic individuals and reproduced them by incubating lipoproteins from healthy individuals with cholic acid. The cholestatic patients showed an increase in low density lipoprotein (LDL) (> 85%), with a smaller proportion of esterified cholesterol, and a fall in high density lipoprotein (HDL) (< 10%), with a larger proportion of phospholipids. The protein composition of cholestatic HDL(1) was characterized by a smaller proportion of apo A (I, II) and a prominent apo E fraction (39% vs. 9%). These changes involved an increase in degree of molecular packing (order) of HDL(1). The addition of cholic acid to serum from healthy individuals altered the lipoprotein distribution, with an increase in LDL, the disappearance of HDL(2) and HDL(3) and the appearance of HDL(1). These HDL(1) were characterized by increased phospholipid and reduced apo AI fractions. They also showed a lower density and appeared as spherical particles in contrast to cholestatic HDL. Incubation of healthy HDL with cholic acid in vitro reproduces some of the alteration observed in cholestatic HDL.