The interplay between cholesterol and inflammation in the evolution of atherosclerosis

Verschuren, L. (2009)

Doctoral Thesis

Atherosclerosis is a multifactorial disease of the large arteries and the leading cause of morbidity and mortality in industrialized countries. There is ample evidence that hypercholesterolemia (i.e. elevated plasma levels apo-B-containing lipoproteins) is a major causative factor in atherogenesis. It is equally clear that atherogenesis has an inflammatory component which is thought to drive the progression of the disease. However, while the lipid component in atherosclerosis development is relatively well-understood, the origin and exact contribution of the inflammatory component remains largely unknown. The aim of this thesis is to further define and delineate the contribution of the inflammatory component to the atherosclerotic process and to elucidate the link between cholesterol and inflammation in atherosclerotic lesion formation and progression. The studies of this thesis show that, besides plasma cholesterol, inflammation contributes to a substantial extent to atherogenesis. Intervention strategies directed at lowering apoB-containing lipoproteins and reducing inflammation may therefore be more effective than current lipid-lowering strategies. Direct experimental evidence for this assumption mainly comes from animal experiments as described in this thesis. Human intervention studies are necessary to evaluate whether these findings can also be translated to the human situation.

• Atherosclerosis
• Cholesterol
• Inflammation
• Mice

• All authors: Verschuren, L.
• Supervisor: Bockel, J.H. van
• Co-supervisor: Kleemann, R.; Kooistra, T.
• Qualification: Doctor (dr.)
• Awarding Institution: Leiden University Medical Center (LUMC), Leiden University
• Date: 2009-01-22
• ISBN (print): 9789071382819
• Sponsorship: The research described in this thesis was supported by a grant of the Netherlands Heart Foundation (NHF-2002B102)