|
Transgenic mouse models have been superb in unravelling the individual genes that govern diet induced atherosclerosis. By applying genome wide expression analysis, we now have the opportunity to better understand atherogenesis as a process characterized by the involvement of multiple genes. Much information has been acquired on the effects of feeding atherogenic diets on the gene expression profile of liver. Our data show the activation of metabolic pathways controlled by nuclear receptors as well as inflammatory pathways. Notably, we show that inflammation and in particular macrophages are a hallmark at already very early stages of fat-feeding. We also looked in more detail at the behaviour of gene expression in macrophages during foam cell formation. Using microarray analysis, it is clear that foam cell formation has a differential effect on inflammatory pathways. In particular, the response to an inflammatory stimulus (LPS) is stronger in foam cells. Additional experiments have examined the role of inflammatory gene expression in foam cell formation by the transcription factor NF-κB in macrophages. We found clear effects of modification of inflammatory NF-κB signalling on pathways regulating macrophage lipid homeostasis. Taken together, it is becoming very clear that there is enormous crosstalk between lipids and inflammatory responses, with the macrophage being a central player.
|
J. Vasc. Biol. 42, Sup:2 (2005) p16