? The major goal of this proposal is to determine how triglyceride-rich lipoproteins (TGRL) and their associated apoprotein E (apoE) isoforms interact with endothelial cell plasma membrane micro domains, including lipid rafts, in the postprandial state. Our proposal spans the spectrum from detection of single molecules affecting lipoprotein-endothelial cell interactions to individual human feeding studies. Work from our lab and others have led us to propose the following specific aims: ? ? Aim 1: To determine the conformational properties of apoE3 and apoE4 present on very-low density lipoproteins (VLDL) in the pre- and postprandial states. ? ? Aim 2: To examine apoE3 and apoE4 interactions with endothelial cells in the pre- and postprandial states. ? ? Aim 3: To determine how the pre- and postprandial states modify plasma membrane microstructure. ? ? We have assembled a unique group with expertise covering structural biology, laser spectroscopy and microscopy, lipid biochemistry, vascular biology and clinical nutrition. The combined expertise of this group will enable us to extend our understanding of how lipoproteins interact with endothelium using advanced imaging techniques at the cellular and molecular level. We expect that the molecular level understanding obtained through the proposed work will mark an important step forward in our basic and clinical understanding of how atherosclerotic cardiovascular disease, the greatest single cause of morbidity and mortality in the U.S., is initiated. ? ? ?
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