Dyslipidemia, inflammation and the link with metabolism in driving atherosclerosis

In this thesis the first part shines a light on how different subsets of lipoproteins affect and drive immune cell inflammation. This part describes how these lipoproteins are involved in inflammation of immune cells and endothelial cells and how the latter facilitates transmigration of monocytes to contribute to the process of atherosclerosis). Next, we describe that LDL induces lipid droplet formation in monocytes and we focus on the role of remnant cholesterol in context of arterial wall inflammation. Subsequently, it is discussed how postprandial inflammation affects monocytes in patients with metabolic syndrome. Finally, the effect of Lp(a) on hematopoietic activity and subsequent monocyte phenotype is investigated.
The second part of this thesis reveals how lipid-induced inflammation is fueled by cellular metabolic alterations. First, the interaction of lipoproteins with immune- and endothelial cells is investigated and subsequently how these cells rewire their metabolism as a response to inflammation is studied. Subsequently, we investigated the potential of OxPL-Lp(a) to induce inflammation in endothelial cells and the ability of these cells to increase glycolysis after Lp(a) exposure. Furthermore, we show that inhibition of glycolysis leads to decreased inflammation in ECs and thereby decreased monocyte transmigration. Next, we reveal that in vivo inhibition of glycolysis in hypercholesterolemic mice leads to decreased atherogenesis and increased plaque stability.