The long term goal of this research is to understand the functional basis for the expression of apolipoprotein (apo) E in peripheral tissues. The proposal consists of 4 aims that are focused on activities of apoE that influence cellular cholesterol metabolism in adrenal cells and activities that are anti-atherogenic within the vascular wall. Experiments in Aim 1 will test the hypothesis that low levels of systemic apoE act within the vascular wall to block an early step in atherosclerotic lesion development.
Aim 2 will explicitly test the hypothesis that low levels of apoE provide protection against atherogenesis initiated by apoB48 lipoproteins but do not protect against atherogenesis due to apoB100 lipoproteins.
Aim 3 will test the hypothesis that adrenal gland apoE expression increases adrenal cholesteryl ester storage and diminishes steroid production.
Aim 4 will test the physiological importance of a newly discovered apoE-stimulated pathway for the selective uptake of low density lipoprotein cholesteryl ester.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Physiological Chemistry Study Section (PC)
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Applebaum-Bowden, Deborah
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State University New York Stony Brook
Schools of Medicine
Stony Brook
United States
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Zhao, Yue; Thorngate, Fayanne E; Weisgraber, Karl H et al. (2005) Apolipoprotein E is the major physiological activator of lecithin-cholesterol acyltransferase (LCAT) on apolipoprotein B lipoproteins. Biochemistry 44:1013-25
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