CHARACTERIZATION OF LIPOPROTEINS DURING HUMAN CHOLESTASIS

We have characterized changes in lipoproteins from cholestatic individ uals and reproduced them by incubating lipoproteins from healthy indiv iduals with cholic acid. The cholestatic patients showed an increase i n 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 composi tion of cholestatic HDL(1) was characterized by a smaller proportion o f apo A (I, II) and a prominent apo E fraction (39% vs. 9%). These cha nges involved an increase in degree of molecular packing (order) of HD L(1). The addition of cholic acid to serum from healthy individuals al tered the lipoprotein distribution, with an increase in LDL, the disap pearance of HDL(2) and HDL(3) and the appearance of HDL(1). These HDL( 1) were characterized by increased phospholipid and reduced apo AI fra ctions. They also showed a lower density and appeared as spherical par ticles in contrast to cholestatic HDL. Incubation of healthy HDL with cholic acid in vitro reproduces some of the alteration observed in cho lestatic HDL.