title: HDL functionality in reverse cholesterol transport--Challenges in translating data emerging from mouse models to human disease.
abstract: Whereas LDL-derived cholesterol accumulates in atherosclerotic lesions, HDL particles are thought to facilitate removal of cholesterol from the lesions back to the liver thereby promoting its fecal excretion from the body. Because generation of cholesterol-loaded macrophages is inherent to atherogenesis, studies on the mechanisms stimulating the release of cholesterol from these cells and its ultimate excretion into feces are crucial to learn how to prevent lesion development or even induce lesion regression. Modulation of this key anti-atherogenic pathway, known as the macrophage-specific reverse cholesterol transport, has been extensively studied in several mouse models with the ultimate aim of applying the emerging knowledge to humans. The present review provides a detailed comparison and critical analysis of the various steps of reverse cholesterol transport in mouse and man. We attempt to translate this in vivo complex scenario into practical concepts, which could serve as valuable tools when developing novel HDL-targeted therapies.
authors.affiliation: Wihuri Research Institute, Helsinki, Finland. Electronic address: miriam.lee@wri.fi.
authors.forename: Miriam
authors.initials: M
authors.lastname: Lee-Rueckert
authors.affiliation: IIB Sant Pau-CIBER de Diabetes y Enfermedades Metabolicas Asociadas, Barcelona, Spain.
authors.forename: Joan Carles
authors.initials: JC
authors.lastname: Escola-Gil
authors.affiliation: Wihuri Research Institute, Helsinki, Finland. Electronic address: petri.kovanen@wri.fi.
authors.forename: Petri T
authors.initials: PT
authors.lastname: Kovanen
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000235:genetics / Q000378:metabolism; D000818:Animals; D016632:Apolipoprotein A-I / Q000235:genetics / Q000378:metabolism; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D001692:Biological Transport; D008076:Cholesterol, HDL / Q000378:metabolism*; D008078:Cholesterol, LDL / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006801:Humans; D006937:Hypercholesterolemia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008049:Lipase / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D013045:Species Specificity
chemical_list: D064286:ATP Binding Cassette Transporter 1; D016632:Apolipoprotein A-I; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D008049:Lipase; D026901:Membrane Transport Proteins; C577833:Abca1 protein, mouse; C482445:Npc1l1 protein, mouse
keywords: Cholesterol efflux; Cholesterol excretion; HDL; Lipid transfer proteins; Reverse cholesterol transport