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- W2912318848 abstract "This thesis reports on the use of neopterin and 7,8-dihydroneopterin as biomarkers of inflammation in advanced atherosclerosis and the use of spectral CT imaging to assess the features and morphology of vulnerable atherosclerotic plaque. New non-invasive imaging modalities are being explored as current methods for the diagnosis of cardiovascular disease cannot be used for subclinical atherosclerosis. Specifically, non-invasive tools are required to assess plaque vulnerability, the main cause of stroke or heart attack. Neopterin has shown promise as biomarker for cardiovascular disease, with both prognostic and diagnostic capabilities. However, despite its known utility as a marker, little is understood about how the neopterin measured in blood plasma or serum relates to the underlying condition and how it relates to plaque vulnerability. Furthermore, it is generally unknown how the parent compound 7,8-dihydroneopterin becomes oxidised in biological systems.In this thesis, live excised carotid plaques from symptomatic patients provided a unique experimental system to test the effects of oxidants and inflammatory stimulants on the inflammatory biomarkers neopterin and 7,8-dihydroneopterin. Activating macrophages in the plaque produced a response that is inversely proportional to the volume of calcification in the tissue. The antioxidant and radical scavenging properties 7,8-dihydroneopterin were explored using a key oxidant, superoxide. Neopterin was found to be a central product of the complex reaction. Baseline 7,8-dihydroneopterin and neopterin values in plaque compared to plasma demonstrated that the plasma values do not necessarily reflect the antioxidant capacity or inflammatory status of the plaque tissue. However, there appears to be good correlation between immune cell activity in plaque and plasma lactate values. Calcification, haemorrhage, and lipid cores were identified using MARS spectral CT. Development of a low-density lipoprotein- based nanoparticle for the identification of macrophages within in plaque had limited success, with more work needed to improve the uptake in a cell model before use in a tissue sample.The results of this thesis demonstrate that spectral imaging has the capability to assess features of plaque vulnerability such as calcium deposition, lipid pools and intraplaque haemorrhage. This has the potential to improve patient diagnosis if this can be translated to human use. Furthermore, 7,8-dihydroneopterin and neopterin are modulated by changes in oxidant levels and immunological stimulation in atherosclerotic tissue, improving support for the case for adding these markers to panel of biomarkers for cardiovascular disease. Further research into how plasma levels of both compounds relative to in situ plaque production impacts patient outcomes would provide insight into the role of antioxidant capacity in plaque vulnerability and atherosclerosis." @default.
- W2912318848 created "2019-02-21" @default.
- W2912318848 creator A5006686513 @default.
- W2912318848 date "2018-01-01" @default.
- W2912318848 modified "2023-09-23" @default.
- W2912318848 title "Atherosclerotic plaque biochemistry and MARS spectral imaging." @default.
- W2912318848 doi "https://doi.org/10.26021/7120" @default.
- W2912318848 hasPublicationYear "2018" @default.
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