Roles for lipid-activated transcription factors in atherosclerosis

The initial cellular event in atherosclerosis is the recruitment of monocytes to the vessel wall, and the formation of foam cells by the uptake of modified lipoproteins. The role of macrophages in this process is the uptake and processing of lipoproteins ultimately leading to foam cell formation. These cells also sustain a chronic inflammatory reaction believed to participate in disease progression. We have been interested in identifying regulatory processes contributing to these events. Some members of a distinct class of transcription factors, nuclear hormone receptors, are expressed in macrophages and are likely to have roles in the initiation of atherosclerosis. We review here the identification of interrelated nuclear receptor-regulated pathways involving peroxisome proliferator-activated receptor, liver X receptor, and retinoid receptors, and contributing to lipid uptake and efflux in macrophages.