Cholesterol efflux from macrophages and other cells.
Foam cell formation by lipid accumulation in macrophages is a prominent finding in atherosclerotic plaques. Since macrophages cannot limit the uptake of lipids, cholesterol efflux is probably essential to inhibit progression and cause regression of atherosclerosis. Cholesterol efflux is generally attributed to HDL in the extracellular space. Slow bidirectional fluxes of cholesterol occur between plasma membrane and lipid-rich HDL subclasses. Esterification of cholesterol in HDL by lecithin: cholesterol acyltransferase causes net cholesterol efflux. In contrast, some lipid-free apolipoproteins (especially apolipoprotein A-I) and lipid-poor HDL subclasses such as prebeta 1-apolipoprotein A-I containing lipoprotein mediate rapid and unidirectional cholesterol efflux from specific cholesterol domains in the plasma membrane. Extracellular presence of HDL or apolipoprotein A-I moreover facilitates the translocation of cholesterol from intracellular pools to the plasma membrane, probably via signal transduction. The activated transfer machinery appears to involve the Golgi apparatus and diverts cholesterol from the shuttle between acylcoenzyme A: cholesterol acyltransferase and neutral cholesteryl ester hydrolase (cholesteryl ester cycle). Endogenously synthesized apolipoprotein E facilitates HDL-mediated cholesterol efflux from macrophages. Moreover, at least in human monocyte-derived macrophages, apolipoprotein E appears to be involved in the export of cholesterol independently from extracellular acceptors. Cholesterol efflux can be inhibited by some oxysterols that are found in macrophages of atherosclerotic plaques and macrophages that are loaded in vitro with oxidized LDL.
von Eckardstein
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Institute of Clinical Chemistry and Laboratory Medicine, Westfälische Wilhelms-Universität Münster, Germany.
D001053:Apolipoproteins / Q000378:metabolism; D001057:Apolipoproteins E / Q000378:metabolism / Q000494:pharmacology; D002352:Carrier Proteins; D002784:Cholesterol / Q000378:metabolism*; D002788:Cholesterol Esters / Q000378:metabolism; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism*; D016601:RNA-Binding Proteins; D018110:Receptors, Lipoprotein / Q000378:metabolism; D013261:Sterols / Q000378:metabolism
D001053:Apolipoproteins; D001057:Apolipoproteins E; D002352:Carrier Proteins; D002788:Cholesterol Esters; D008075:Lipoproteins, HDL; D016601:RNA-Binding Proteins; D018110:Receptors, Lipoprotein; D013261:Sterols; C031616:high density lipoprotein receptors; C075197:high density lipoprotein binding protein; D002784:Cholesterol