The aim of this thesis was to unravel a selection of a multitude of potential causal pathways that may underlie the association between excess body fat and cardiovascular disease, such as... Show moreThe aim of this thesis was to unravel a selection of a multitude of potential causal pathways that may underlie the association between excess body fat and cardiovascular disease, such as adipokines, inflammation, HDL-cholesterol and postprandial triglyceride response, and cholesteryl ester transfer protein (CETP). We showed that hs-CRP and GlycA as measures of inflammation, adiponectin, and leptin are not associated with clinical and subclinical cardiovascular disease in the general population. However, all may be relevant markers of disease risk. Also, postprandial triglyceride excursions, genetically-determined CETP and HDL-cholesterol, while not related with subclinical atherosclerosis in the general population, may be interesting targets to pursue in women and men separately, and in subgroups of individuals at high-cardiovascular risk. Show less
Atherosclerosis is the underlying cause of most cardiovascular diseases. The evidence to support a cholesterol-atherosclerosis link has been revealed in the past three decades. There is a growing... Show moreAtherosclerosis is the underlying cause of most cardiovascular diseases. The evidence to support a cholesterol-atherosclerosis link has been revealed in the past three decades. There is a growing consensus that therapeutic lowering of plasma VLDL- and LDL-cholesterol levels and raising of HDL-cholesterol level will reduce the risk of cardiovascular incidence. This dissertation is dedicated to the regulation of lipid metabolism pathways, both in plasma and liver, and its subsequent effects on atherosclerotic lesion progression and regression. The first part of the thesis focuses on the hepatic lipid metabolism and the pharmaceutical interventions in the liver. The second part of the thesis focuses on the concept of atherosclerotic lesion regression, shedding insights in the role of LXR activation and application of mouse models in regression studies. In Chapter 8, the results obtained from all the experiments mentioned above are summarized and discussed with respect to the implications of these studies for future investigations. Show less
