The overall goal of this program project is to test the contribution of changes in high density lipoprotein (HDL) function in human disease, specifically atherosclerosis. One of the major hypotheses tested is that the lipid peroxidation that occurs during various condition that increase the risk for atherosclerosis (e.g. familial hypercholesterolemia and chronic kidney disease) causes HDL to become modified by reactive lipid dicarbonyls and that these modifications markedly alter HDL function. This core will provide synthetic versions of these reactive dicarbonyls to project investigators so that they can test the effects of HDL modification. This core will also provide synthetic compounds that act as dicarbonyl scavengers and that can be used in both cultured cells, in animals, and in humans to block the reaction of dicarbonys with proteins and phosphatidylethanolamine. These scavengers are useful both to test the contribution of these dicarbonyls and as potential medicinal agents. Finally, this core will measure dicarbonyl adducts on proteins and phosphatidylethanolamine.
Aim 1 : Synthesize IsoLG and other dicarbonyls for testing in cultured cell and animal models.
Aim 2 : Synthesize dicarbonyl scavengers for testing in cultured cell and animal models.
Aim 3 : Measure the amounts of dicarbonyl modified proteins and phosphatidylethanolamines that are formed in tissue samples and fluids in animal models and humans with disease.
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|Sedgeman, Leslie R; Beysen, Carine; Allen, Ryan M et al. (2018) Intestinal bile acid sequestration improves glucose control by stimulating hepatic miR-182-5p in type 2 diabetes. Am J Physiol Gastrointest Liver Physiol :|
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