The long-term goal of this research is to understand better the regulation of plasma cholesterol and low density lipoprotein (LDL) concentrations. Elevated LDL is one of the factors associated with coronary heart disease and with familial hypercholesterolemia (FH). Our research will focus on lipoprotein receptors in tissues and cultured cells which might help to regulate plasma lipoproteins. Two receptors will be considered, a newly-found receptor of HepG2 liver cells, and the LDL receptor. The receptors will be purified from human cells and factors important in their control will be determined. FH is a disorder in which plasma LDL levels are too high because of deficient tissue LDL receptors. Recent work strongly suggests that LDL receptors are present in cells from FH patients, but are not adequately expressed. In order to understand FH better, the regulation of normal cell receptors will be studied and the finding compared to FH cells. In addition, polymorphism in LDL receptors will be studied in normal individuals and in patients with hyperlipidemias other than FH. Techniques used will include analysis of the binding and degradation of radioiodinated lipoproteins to cells, protein blotting with lipoproteins and antibodies used as detecting agents, protein purification and affinity chromatography, and the preparation of monoclonal antibodies.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL029229-05
Application #
3340336
Study Section
Metabolism Study Section (MET)
Project Start
1986-04-01
Project End
1989-03-31
Budget Start
1987-04-01
Budget End
1988-03-31
Support Year
5
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Washington University
Department
Type
Schools of Medicine
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
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Ostlund Jr, R E; Yang, J W; Heath-Monnig, E et al. (1994) Increased low density lipoprotein receptor expression mediated through the insulin-like growth factor-I receptor in cultured fibroblasts. Mol Endocrinol 8:904-9
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Ostlund Jr, R E (1993) A minimal model for human whole body cholesterol metabolism. Am J Physiol 265:E513-20
Ostlund Jr, R E; McGill, J B; Herskowitz, I et al. (1993) D-chiro-inositol metabolism in diabetes mellitus. Proc Natl Acad Sci U S A 90:9988-92
Ostlund Jr, R E; Matthews, D E (1993) [13C]cholesterol as a tracer for studies of cholesterol metabolism in humans. J Lipid Res 34:1825-31
Bosner, M S; Ostlund Jr, R E; Osofisan, O et al. (1993) Assessment of percent cholesterol absorption in humans with stable isotopes. J Lipid Res 34:1047-53
Levy, R; Ostlund Jr, R E; Schonfeld, G et al. (1992) Cholesteryl ester storage disease: complex molecular effects of chronic lovastatin therapy. J Lipid Res 33:1005-15
Ostlund Jr, R E; Staten, M A; Kohrt, W M et al. (1991) Insulin-like growth factor and apolipoprotein B. JAMA 266:1937-8

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