Doctor of Philosophy (PhD)
Gradual deposits of lipids, proteins, and calcium on the coronary arterial walls cause atherosclerosis, leading to blockage of the blood flow and possible heart attack. Despite many studies, the mechanism underlying these processes remains unclear. In this research, differences between native and bypass plaque deposits from the same heart were examined. In addition, the crystalline and the amorphous plaques within these native and bypass vessels were characterized. The techniques used to characterize the deposits included inductively coupled plasma mass spectrometry (ICPMS), solid-state nuclear magnetic resonance (NMR), high performance liquid chromatography (HPLC), etc. The results from the ICPMS technique showed that the concentrations of Ca and P varied widely in the bypass arteries. In contrast, the concentrations of Ca and P were higher in the native deposits. The molar ratios of Ca/P indicated that these elements probably exist as hydroxyapatite in the calcified tissues. However, the molar ratio of Ca/P in the soft tissue suggests that the phosphorus does not only exist as hydroxyapatite but that at least half of it may also be organic. The 13C and 31P solid-states NMR spectra of the native and bypass coronary plaques from the same heart indicated that the concentrations of carbonyl groups, typical of cholesterol esters, were similar between the native and bypass arteries. Significant signals of carbonyl groups in the crystalline and amorphous plaques were due to amino acids and proteins deposited in the plaques. Studies of 31P showed that the phosphorus exists mostly as hydroxyapatite in the crystalline native plaque, but a large proportion exists as organic phosphorus. To study the interactions of calcium with homocysteine and cholesterol, 13C solid-state NMR of homocysteine, Ca-homocysteine, Ca-homocysteine-cholesterol, Ca-cholesterol were performed. Significant spectral changes were also noted when calcium was added to homocysteine and cholesterol. The chemical forms and the distribution of calcium were studied using x-ray absorption and light microscopy with silver staining. Finally, chromatographic methods (CEC and APCI-MS) showed that only 40 % or less of the plaque in native or bypass arteries consisted of cholesterol and its esters and the remaining, 60% were composed of proteins, fatty acids, and phospholipids.
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Thiam, Serigne, "Characterization of native and bypass human coronary artery plaque deposits from the same heart: investigation of the chemical form of calcium in human coronary artery plaque deposits" (2003). LSU Doctoral Dissertations. 612.
Isiah M. Warner