Atherosclerosis is the main underlying pathology of cardiovascular disease. Atherosclerosis is caused by an immune response which is directed against (modified) lipoproteins which accumulate in the... Show moreAtherosclerosis is the main underlying pathology of cardiovascular disease. Atherosclerosis is caused by an immune response which is directed against (modified) lipoproteins which accumulate in the vessel wall. Over time, this accumulation of lipids and immune cells induce morphological abnormalities in the vessel wall which cause the vessel lumen to narrow. This narrowing of the lumen (stenosis) causes ischemia in the downstream tissue. Prolonged ischemia causes myocardial ischemia and/or stroke. The research described in my thesis examines a well-recognized risk factor of atherosclerosis, being dyslipidemia, from an entirely new perspective. More specifically, it describes how dyslipidemia affects intrinsic metabolic processes in T cells, the conductors of the immune response characterizing atherosclerosis, and how this affects their function. My research has contributed to knowledge on the pathophysiology of atherosclerosis and might one day pave the way for the development of novel therapeutic approaches to treat cardiovascular disease. Show less
In this thesis, metabolomics is used to study the role of the host-virus interaction on a metabolic level. A special emphasis is directed on the role of inflammation and oxidative stress on... Show more In this thesis, metabolomics is used to study the role of the host-virus interaction on a metabolic level. A special emphasis is directed on the role of inflammation and oxidative stress on the metabolic level, as part of the innate immune response against viral infection. We chose respiratory syncytial virus (RSV) and hepatitis B virus (HBV) as candidate viruses to metabolically study their role in acute respiratory infection and chronic hepatitis B infection. Secondly we also investigated infant metabolic and immunological consequences of in utero exposure to antiretroviral intervention and human immunodeficiency virus (HIV). Collectively, established targeted metabolomics approaches in conjunction with newly developed metabolomics methodologies and complemented with other “omics” techniques, were used to address pertinent questions related to host metabolic functioning and alterations during viral infection. In vitro RSV studies together with in vivo patient based studies relating to chronic HBV infection and in utero exposure too antiretroviral and HIV were used to address these questions. The work is divided into three research parts containing: i. the analytical methodology development work, ii. in vitro based metabolomics and iii. patient based metabolomics. Show less
