Dependence of metabolic and structural heterogeneity of cholesterol ester-rich very low density lipoproteins on the duration of cholesterol feeding in rabbits.
Cholesterol ester-rich (CER) VLDL accumulate rapidly in the plasma of rabbits fed cholesterol-enriched diets. However, the major loci of enhanced synthesis of subfractions of CER-VLDL, their interaction with macrophages, and their relative contribution to atherogenesis have not yet been elucidated. To determine whether anabolism is hepatic or intestinal, subfractions of CER-VLDL were characterized at selected intervals from day 0 to 60 of cholesterol feeding. Rate zonal ultracentrifugation of CER-VLDL from rabbits fed cholesterol for 4 and 60 d demonstrated an early increase of the proportion of cholesterol carried in the intestinally-derived fraction (designated as Fx-I) of VLDL compared with that in hepatically-derived particles (Fx-H). Quantification by size exclusion HPLC also demonstrated that Fx-I was a prominent CER-VLDL component at day 4, while Fx-H particles became increasingly prominent with further cholesterol feeding. At both 4 and 60 d Fx-I stimulated cholesterol esterification and intracellular cholesterol content in macrophages more than the corresponding Fx-H did. In fact, Fx-H harvested at 4 d produced no cholesterol ester deposition. In contrast, Fx-H harvested at 60 d markedly stimulated cholesterol esterification and intracellular cholesterol content. Thus, both compositional and metabolic characteristics of CER-VLDL changed as a function of the duration cholesterol feeding.
Daugherty
A
A
Cardiovascular Division, Washington University School of Medicine, St. Louis, Missouri 63110.
Oida
K
K
Sobel
B E
BE
Schonfeld
G
G
D000818:Animals; D001161:Arteriosclerosis / Q000097:blood / Q000209:etiology; D005591:Chemical Fractionation; D002788:Cholesterol Esters / Q000097:blood / Q000378:metabolism* / Q000502:physiology; D002791:Cholesterol, Dietary / Q000008:administration & dosage*; D002851:Chromatography, High Pressure Liquid; D004587:Electrophoresis, Agar Gel; D006937:Hypercholesterolemia / Q000097:blood / Q000209:etiology; D008079:Lipoproteins, VLDL / Q000097:blood / Q000378:metabolism* / Q000502:physiology; D008264:Macrophages / Q000378:metabolism; D011817:Rabbits; D013329:Structure-Activity Relationship; D013997:Time Factors
D002788:Cholesterol Esters; D002791:Cholesterol, Dietary; D008079:Lipoproteins, VLDL