The infiltration of monocytes in the arterial wall, their maturation to macrophages, and the subsequent accumulation of cholesterol in these macrophages initiate the process of atherosclerosis. We studied the importance of specific genes in macrophages for atherosclerotic lesion formation by means of bone marrow transplantation. Recipient mice, used as model for atherosclerosis, are LDL-receptor knock-out mice. Macrophages can become foam cells as a result of a disturbed balance between the uptake of cholesterol from lipoproteins and cholesterol efflux. ABCA1 and ABCG1 are two cholesterol transporters that may act sequentially to remove cellular cholesterol. The combined deletion of macrophage ABCA1 and ABCG1 leads to massive lipid accumulation in tissue macrophages. The tested mice exhibit severe plasma hypocholesterolemia, and despite the massive foam cell formation of tissue macrophages, no lipid accumulation was observed in the vascular wall. It is concluded that, because of their  hypocholesterolemia, the mice lack the trigger to attract macrophages to the arterial wall. The role of scavenger-receptor BI, the HDL receptor, was further analyzed and it appears that VLDL can also interact  with SR-BI. Deficiency of SR-BI in adrenals impairs an adequate adrenal glucocorticoid-mediated stress response to fasting.

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