Lipoproteins, macrophage function, and atherosclerosis: Beyond the foam cell?

Atherogenesis requires and is highly influenced by the interaction between lipoproteins and macrophages. Most of the focus to date has been on the ability of atherogenic lipoproteins (such as low-density lipoproteins, LDL) to promote and of anti-atherogenic lipoproteins (such as high-density lipoproteins, HDL) to prevent the development of the cholesteryl ester-enriched macrophage-derived foam cell. However, lipoprotein-macrophage interactions have the potential to modulate macrophage function in a variety of additional ways that may impact on atherosclerosis. These include modulating cellular cholesterol and oxysterol content, providing fatty acids as ligands for PPARs, and acting as ligands for macrophage scavenger and Toll-like receptors. We suggest that atherogenic lipoproteins promote and anti-atherogenic lipoproteins inhibit atherogenesis by modulating macrophage function in a variety of ways beyond cholesteryl ester accumulation and foam cell formation. Atherogenesis requires and is highly influenced by the interaction between lipoproteins and macrophages. Most of the focus to date has been on the ability of atherogenic lipoproteins (such as low-density lipoproteins, LDL) to promote and of anti-atherogenic lipoproteins (such as high-density lipoproteins, HDL) to prevent the development of the cholesteryl ester-enriched macrophage-derived foam cell. However, lipoprotein-macrophage interactions have the potential to modulate macrophage function in a variety of additional ways that may impact on atherosclerosis. These include modulating cellular cholesterol and oxysterol content, providing fatty acids as ligands for PPARs, and acting as ligands for macrophage scavenger and Toll-like receptors. We suggest that atherogenic lipoproteins promote and anti-atherogenic lipoproteins inhibit atherogenesis by modulating macrophage function in a variety of ways beyond cholesteryl ester accumulation and foam cell formation.