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.
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|Temel, Ryan E; Parks, John S; Williams, David L (2003) Enhancement of scavenger receptor class B type I-mediated selective cholesteryl ester uptake from apoA-I(-/-) high density lipoprotein (HDL) by apolipoprotein A-I requires HDL reorganization by lecithin cholesterol acyltransferase. J Biol Chem 278:4792-9|
|Thorngate, Fayanne E; Strockbine, Penelope A; Erickson, Sandra K et al. (2002) Altered adrenal gland cholesterol metabolism in the apoE-deficient mouse. J Lipid Res 43:1920-6|
|Swarnakar, S; Beers, J; Strickland, D K et al. (2001) The apolipoprotein E-dependent low density lipoprotein cholesteryl ester selective uptake pathway in murine adrenocortical cells involves chondroitin sulfate proteoglycans and an alpha 2-macroglobulin receptor. J Biol Chem 276:21121-8|
|DeMattos, R B; Rudel, L L; Williams, D L (2001) Biochemical analysis of cell-derived apoE3 particles active in stimulating neurite outgrowth. J Lipid Res 42:976-87|
|Thorngate, F E; Rudel, L L; Walzem, R L et al. (2000) Low levels of extrahepatic nonmacrophage ApoE inhibit atherosclerosis without correcting hypercholesterolemia in ApoE-deficient mice. Arterioscler Thromb Vasc Biol 20:1939-45|
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