ATHEROSCLEROSIS AND PERIPHERAL APOPROTEIN E SYNTHESIS

State University New York Stony Brook, Stony Brook NY

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Abstract

DESCRIPTION (Adapted from applicant's abstract): 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.