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Abstract: 620 MACROPHAGE CHOLESTEROL HOMEOSTASIS AND ATHEROGENESIS
Workshop IV-8 - Basic Science and Vascular Biology: Lipoproteins, Macrophages and Atherosclerosis Abstract: 620 Citation: Atherosclerosis Supplement 2009, Vol. 10, Issue 2
MACROPHAGE CHOLESTEROL HOMEOSTASIS AND ATHEROGENESIS T van Berkel, Y Zhao, R Hildebrand, R Out, M Hoekstra, I Meurs, M van Eck LACDR - Biopharmaceutics, Leiden University, Leiden, Zuid-Holland Deposition of excessive amounts of cholesteryl esters in macrophages of the arterial wall, leading to foam cell formation, is a key event in atherogenesis. Macrophage cholesterol homeostasis involves a delicate balance between lipid influx and lipid efflux. Macrophages are incapable of limiting the uptake of lipids via scavenger receptors and therefore largely depend on cholesterol efflux pathways to maintain cellular lipid homeostasis. Important mediators of macrophage cholesterol efflux are ABCA1, which mediates the efflux of cholesterol to lipid-poor apo A-I. Furthermore ABCG1 and SR-BI can efflux cholesterol to mature HDL. As a consequence of compensatory mechanisms, the single ABCA1, ABCG1 or SR-BI deficiency in macrophages only leads to moderate effects on cholesterol efflux and atherogenesis. Combined deletion of ABCA1 and ABCG1 leads to massive lipid accumulation and foam cell formation of tissue macrophages, while massive foam cell formation, atherosclerotic lesion development and inflammation is also observed by combined deletion of macrophage ABCA1 and SR-BI. The combined macrophage deletions of ABCA1, ABCG1 and/or SR-BI show the essential function of these cholesterol transporters in macrophage foam cell formation and atherosclerotic lesion development.
MACROPHAGE CHOLESTEROL HOMEOSTASIS AND ATHEROGENESIS T van Berkel, Y Zhao, R Hildebrand, R Out, M Hoekstra, I Meurs, M van Eck LACDR - Biopharmaceutics, Leiden University, Leiden, Zuid-Holland Deposition of excessive amounts of cholesteryl esters in macrophages of the arterial wall, leading to foam cell formation, is a key event in atherogenesis. Macrophage cholesterol homeostasis involves a delicate balance between lipid influx and lipid efflux. Macrophages are incapable of limiting the uptake of lipids via scavenger receptors and therefore largely depend on cholesterol efflux pathways to maintain cellular lipid homeostasis. Important mediators of macrophage cholesterol efflux are ABCA1, which mediates the efflux of cholesterol to lipid-poor apo A-I. Furthermore ABCG1 and SR-BI can efflux cholesterol to mature HDL. As a consequence of compensatory mechanisms, the single ABCA1, ABCG1 or SR-BI deficiency in macrophages only leads to moderate effects on cholesterol efflux and atherogenesis. Combined deletion of ABCA1 and ABCG1 leads to massive lipid accumulation and foam cell formation of tissue macrophages, while massive foam cell formation, atherosclerotic lesion development and inflammation is also observed by combined deletion of macrophage ABCA1 and SR-BI. The combined macrophage deletions of ABCA1, ABCG1 and/or SR-BI show the essential function of these cholesterol transporters in macrophage foam cell formation and atherosclerotic lesion development.