EXOGENOUS SUPPLY OF ARTIFICIAL LIPOPROTEINS DOES NOT DECREASE SUSCEPTIBILITY TO ATHEROSCLEROSIS IN CHOLESTEROL-FED RABBITS

We investigated the effects of reconstituted apo A-I-containing high-d ensity lipoprotein (r-HDL, homologous to small pre-beta-migrating HDL) and reconstituted triglyceride-rich lipoprotein (r-TRL, a mixture of Intralipid(R) and apo E) on atherogenesis in rabbits fed a 0.5% choles terol diet for 8 weeks. Male Japanese white rabbits (n = 17) were divi ded into three groups: the control group (n = 7) received a placebo an d 2.5 ml of Intralipid(R) 20 h later; the second group (n = 6) receive d r-HDL containing 18 mg of apo A-I followed by 2.5 mi of Intralipid(R ) and the third group (n = 4) received 18 mg of r-HDL and 2.5 ml of r- TRL containing 4 mg of apo E. Rabbits were injected with the agents we ekly and the same interval (20 h) was maintained between the two injec tions. Three minutes after the injection of r-HDL, a sharp increase in the pre-beta-migrating fraction was observed. The cholesterol-rich di et similarly increased serum lipids in the three groups. No significan t changes of the HDL cholesterol and apo A-I concentrations were obser ved in the three groups. Conversely, there was a 12-fold increase of a po E which correlated positively with the total cholesterol level. Inj ection of r-HDL and r-TRL caused slight inhibition of fatty streak dev elopment and lipid deposition in the aortic wall, but neither change w as statistically significant. Lipid accumulation in the liver was simi lar in all three groups. These results suggest that the physiological properties of artificial and native lipoproteins may differ.