Macrophage cholesterol transport: a critical player in foam cell formation.
Mammalian cells have evolved complex feedback mechanisms to ensure sufficient supply of cholesterol and to prevent its excessive accumulation. During the process of atherosclerosis, these homeostatic mechanisms fail in macrophages. Uncontrolled cholesterol deposition is promoted by scavenger functions of the macrophages and the adaptive mechanisms elicited are not sufficient to process the lipid load. Consequently, a lipid-laden 'foam cell' is formed. In this review, we summarize key aspects of intracellular cholesterol processing in the special case of macrophages, including mechanisms of lipoprotein cholesterol uptake, fate of the internalized cholesterol and mechanisms implicated in cholesterol efflux. The importance of inflammatory cues, the cellular compartmentalization of cholesterol homeostatic responses and the increasing information on the transcriptional control of cholesterol balance are discussed.
Vainio
Saara
S
Department of Molecular Medicine, National Public Health Institute, Biomedicum Helsinki, Haartmaninkatu 8, Fl-00251 Helsinki, Finland.
Ikonen
Elina
E
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000818:Animals; D016632:Apolipoprotein A-I / Q000096:biosynthesis; D001057:Apolipoproteins E / Q000096:biosynthesis; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism*; D002788:Cholesterol Esters / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D005487:Foam Cells / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D000071518:Liver X Receptors; D008264:Macrophages / Q000378:metabolism*; D008565:Membrane Proteins; D057093:Orphan Nuclear Receptors; D010446:Peptide Fragments / Q000096:biosynthesis; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis; D011971:Receptors, Immunologic / Q000378:metabolism; D011973:Receptors, LDL / Q000378:metabolism; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors / Q000096:biosynthesis
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D016632:Apolipoprotein A-I; D001057:Apolipoproteins E; D022762:CCAAT-Enhancer-Binding Proteins; D002788:Cholesterol Esters; D004268:DNA-Binding Proteins; D000071518:Liver X Receptors; D008565:Membrane Proteins; D057093:Orphan Nuclear Receptors; D010446:Peptide Fragments; D018160:Receptors, Cytoplasmic and Nuclear; D011971:Receptors, Immunologic; D011973:Receptors, LDL; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C497387:SREBF1 protein, human; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors; C117630:apolipoprotein E (141-155); D002784:Cholesterol