Apoprotein E serves important functions in the recognition of triglyceride-rich lipoprotein remnants by hepatic and peripheral cells. The """"""""wild type"""""""" apoE molecule (apoE3) binds to cellular apoB, E receptors with greater affinity than does LDL, whereas the interactions of certain mutant apoE molecules (e.g., apoE2) with cells are grossly impaired. The hypothesis to be tested is that the plasma lipoproteins of individuals who are apoE2/E3 heterozygotes are more responsive to alterations of dietary lipids than are the plasma lipoproteins of otherwise similar individuals who are apoE3/E3 homozygotes. Plasma lipoproteins will be characterized in the two groups of subjects while they are eating habitual, basal and high fat, high cholesterol experimental diets, using zonal ultracentrifugation and gel permeation column chromatography. Plasma lipoprotein lipids and apoprotein concentrations will be quantified and lipid and apoprotein compositions of lipoprotein fractions will be obtained. ApoE2/E3 heterozygotes comprize about 25% of the American population. Therefore, if apoE2/E3 heterozygotes turn out to be diet """"""""hyperresponders"""""""", an important segment of the population presumably at higher than average risk for the development of diet-related atherosclerosis will have been identified. Steps then can be taken to find and intervene on such individuals. A secondary hypothesis relating to the responsiveness of plasma lipoproteins to changes in dietary patterns of young and older subjects also will be tested, if time and resources permit.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
Project #
Application #
Study Section
Nutrition Study Section (NTN)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Washington University
Schools of Medicine
Saint Louis
United States
Zip Code
Jiao, S; Cole, T G; Kitchens, R T et al. (1990) Genetic heterogeneity of plasma lipoproteins in the mouse: control of low density lipoprotein particle sizes by genetic factors. J Lipid Res 31:467-77
Keidar, S; Goldberg, A C; Cook, K et al. (1990) A high carbohydrate-fat free diet alters the proportion of heparin-bound VLDL in plasma and the expression of VLDL-apoB-100 epitopes. Metabolism 39:281-8
Jiao, S; Cole, T G; Kitchens, R T et al. (1990) Genetic heterogeneity of lipoproteins in inbred strains of mice: analysis by gel-permeation chromatography. Metabolism 39:155-60
Daugherty, A; Oida, K; Sobel, B E et al. (1988) Dependence of metabolic and structural heterogeneity of cholesterol ester-rich very low density lipoproteins on the duration of cholesterol feeding in rabbits. J Clin Invest 82:562-70
Kleinman, Y; Krul, E S; Burnes, M et al. (1988) Lipolysis of LDL with phospholipase A2 alters the expression of selected apoB-100 epitopes and the interaction of LDL with cells. J Lipid Res 29:729-43
Schonfeld, G (1988) Dietary treatment of hyperlipidemia. Clin Chem 34:B111-4
Krul, E S; Tikkanen, M J; Schonfeld, G (1988) Heterogeneity of apolipoprotein E epitope expression on human lipoproteins: importance for apolipoprotein E function. J Lipid Res 29:1309-25
Daugherty, A; Zweifel, B S; Sobel, B E et al. (1988) Isolation of low density lipoprotein from atherosclerotic vascular tissue of Watanabe heritable hyperlipidemic rabbits. Arteriosclerosis 8:768-77
Schonfeld, G; Krul, E S (1986) Immunologic approaches to lipoprotein structure. J Lipid Res 27:583-601
Lo, G S; Goldberg, A P; Lim, A et al. (1986) Soy fiber improves lipid and carbohydrate metabolism in primary hyperlipidemic subjects. Atherosclerosis 62:239-48

Showing the most recent 10 out of 12 publications