- Translating lipid-driven inflammation in atherosclerosis
- Award date
- 4 October 2016
- Number of pages
- Document type
- PhD thesis
- Faculty of Medicine (AMC-UvA)
The first part of this thesis illustrates the increased inflammatory activity present in multiple compartments in patients with atherosclerosis, visualized with functional imaging. Positron emission tomography with computed tomography (PET/CT) is a nuclear technique that employs radioactive tracers, such as the glucose analogue ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG).
Uptake of this tracer marks cellular glucose consumption, and as such, the metabolic need of a cell. Several cell types are known for their high metabolic demands, including proliferative and inflammatory cells. Considering the large number of inflammatory cells in plaques, predominantly macrophages, ¹⁸F-FDG PET/CT is also an attractive strategy in atherosclerosis.
In fact, several histological, plaque gene expression and biomarker studies have validated arterial ¹⁸F-FDG uptake as a surrogate for (macrophage-driven) inflammation.
Having witnessed the correlations between lipids and inflammation in plaque, plasma and progenitors, the second part of this thesis further investigates the direct impact of atherogenic lipoproteins on inflammation by integrating functional imaging with immunological assays. To summarize the major findings in part II, atherogenic lipids and its associated oxidized phospholipid content directly affect inflammation both at the level of the arterial wall as the circulating cells in the plasma compartment. Considering the increased inflammatory activity in patients, despite standard of care including lipid lowering, the final part of this thesis addresses inflammation as a potential additional target in atherosclerosis. In aggregate, the studies in part III of this thesis illustrate the challenges and opportunities of anti-inflammatory drugs in atherosclerosis, in which nanotechnology might facilitate the pursuit for selective and targeted approaches.
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