| Disorders in the metabolism of serum lipids and lipoproteins are critical to the development of atherosclerosis, one of the leading causes of death in the world. The lipoprotein particles in blood plasma or serum are classified by their size and density as very low-density lipoprotein (VLDL), low-density lipoprotein (LDL) and high-density lipoprotein (HDL). They consist largely of a lipid core of nonpolar triacylglycerides and cholesteryl esters surrounded by more polar phospholipids, cholesterol, and apoproteins. The levels of VLDL and LDL, especially oxidized LDL, are positively associated with coronary heart disease (CHD) and thus are considered as atherogenic lipoproteins, whereas HDL is antiatherogenic because of its negative association with CHD. Nuclear magnetic resonance (NMR) spectroscopy has been used to characterize the macromolecules in blood plasma. In this dissertation, NMR approach was used to study interaction of ibuprofen, a promising drug for treatment of atherosclerosis, and lipoproteins in intact human blood serum, to study NMR-invisible metabolites in blood serum and for measurement of pH values.Recent studies have suggested that ibuprofen inhibits LDL oxidation in a high dose-dependent manner and is a promising drug for treatment of the conditions associated with atherosclerosis. In Chapter Two, we present the NMR spectroscopic evidence for the interaction between ibuprofen and phospholipids in lipoprotein particles in intact human plasma. Ibuprofen caused chemical shift up-field drifts for the protons of -N+(CH3)3 moieties of phosphatidylcholine and sphingomyelin, olefinic chains (-CH=CH-,–CH=CHCH2CH=CH-, -(CH2)nCH2CH=), and of (CH2)n and CH3 groups, from unsaturated lipids in lipoprotein particles. The ibuprofen may directly interact with the above-mentioned groups of the phospholipids or induce structural changes for lipoproteins. This may shed light on the mechanism of the drug to protect against the oxidative modification of lipoproteins.
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