The proposed studies will investigate whether fatty acid type and vitamin E concentrations modulate: (1) the amounts of lipid oxidation products isolated from atherosclerotic plaques, and (2) the mechanisms that lead to the formation of lipid oxidation products. NZW rabbits will be maintained on diets enriched in saturated, monounsaturated or n-6 polyunsaturated fat. The diets will contain either high or low concentrations of vitamin E. GC-MS will be used to characterize lipid oxidation products and to infer the mechanisms leading to oxidation assuming that mono-peroxidation products of oleic acid, 3-nitrotyrosine and 3-chlorotyrosine reflect initiation of oxidation by peroxynitrite, free transition metals or Myeloperoxidase, respectively.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL060079-03
Application #
6183865
Study Section
Nutrition Study Section (NTN)
Project Start
1998-08-01
Project End
2002-07-31
Budget Start
2000-08-01
Budget End
2002-07-31
Support Year
3
Fiscal Year
2000
Total Cost
$169,837
Indirect Cost
Name
Wake Forest University Health Sciences
Department
Biochemistry
Type
Schools of Medicine
DUNS #
937727907
City
Winston-Salem
State
NC
Country
United States
Zip Code
27157
Zabalawi, Manal; Bhat, Shaila; Loughlin, Tara et al. (2003) Induction of fatal inflammation in LDL receptor and ApoA-I double-knockout mice fed dietary fat and cholesterol. Am J Pathol 163:1201-13
Li, Hui-Hua; Lyles, Douglas S; Pan, Wei et al. (2002) ApoA-I structure on discs and spheres. Variable helix registry and conformational states. J Biol Chem 277:39093-101
Sorci-Thomas, Mary G; Thomas, Michael J (2002) The effects of altered apolipoprotein A-I structure on plasma HDL concentration. Trends Cardiovasc Med 12:121-8
DeLong, C J; Baker, P R; Samuel, M et al. (2001) Molecular species composition of rat liver phospholipids by ESI-MS/MS: the effect of chromatography. J Lipid Res 42:1959-68
Thomas, M J; Chen, Q; Zabalawi, M et al. (2001) Is the oxidation of high-density lipoprotein lipids different than the oxidation of low-density lipoprotein lipids? Biochemistry 40:1719-24
Li, H H; Thomas, M J; Pan, W et al. (2001) Preparation and incorporation of probe-labeled apoA-I for fluorescence resonance energy transfer studies of rHDL. J Lipid Res 42:2084-91
Thomas, M J; Chen, Q; Sorci-Thomas, M G et al. (2001) Isoprostane levels in lipids extracted from atherosclerotic arteries of nonhuman primates. Free Radic Biol Med 30:1337-46
Thomas, M J (2000) Physiological aspects of low-density lipoprotein oxidation. Curr Opin Lipidol 11:297-301
Li, H; Lyles, D S; Thomas, M J et al. (2000) Structural determination of lipid-bound ApoA-I using fluorescence resonance energy transfer. J Biol Chem 275:37048-54
Thomas, M J (2000) The role of free radicals and antioxidants. Nutrition 16:716-8