title: 9-cis β-Carotene Increased Cholesterol Efflux to HDL in Macrophages.
abstract: Cholesterol efflux from macrophages is a key process in reverse cholesterol transport and, therefore, might inhibit atherogenesis. 9-cis-β-carotene (9-cis-βc) is a precursor for 9-cis-retinoic-acid (9-cis-RA), which regulates macrophage cholesterol efflux. Our objective was to assess whether 9-cis-βc increases macrophage cholesterol efflux and induces the expression of cholesterol transporters. Enrichment of a mouse diet with βc from the alga Dunaliella led to βc accumulation in peritoneal macrophages. 9-cis-βc increased the mRNA levels of CYP26B1, an enzyme that regulates RA cellular levels, indicating the formation of RA from βc in RAW264.7 macrophages. Furthermore, 9-cis-βc, as well as all-trans-βc, significantly increased cholesterol efflux to high-density lipoprotein (HDL) by 50% in RAW264.7 macrophages. Likewise, food fortification with 9-cis-βc augmented cholesterol efflux from macrophages ex vivo. 9-cis-βc increased both the mRNA and protein levels of ABCA1 and apolipoprotein E (APOE) and the mRNA level of ABCG1. Our study shows, for the first time, that 9-cis-βc from the diet accumulates in peritoneal macrophages and increases cholesterol efflux to HDL. These effects might be ascribed to transcriptional induction of ABCA1, ABCG1, and APOE. These results highlight the beneficial effect of βc in inhibition of atherosclerosis by improving cholesterol efflux from macrophages.
authors.affiliation: The Bert W. Strassburger Lipid Center, Sheba Medical Center, Tel-Hashomer 5265601, Israel. sapirula@gmail.com.|Sackler School of Medicine, Tel-Aviv University, Tel Aviv 6997801, Israel. sapirula@gmail.com.
authors.forename: Sapir
authors.initials: S
authors.lastname: Bechor
authors.affiliation: The Bert W. Strassburger Lipid Center, Sheba Medical Center, Tel-Hashomer 5265601, Israel. noazolb@gmail.com.|Sackler School of Medicine, Tel-Aviv University, Tel Aviv 6997801, Israel. noazolb@gmail.com.
authors.forename: Noa
authors.initials: N
authors.lastname: Zolberg Relevy
authors.affiliation: The Bert W. Strassburger Lipid Center, Sheba Medical Center, Tel-Hashomer 5265601, Israel. harari.ayelet1@gmail.com.
authors.forename: Ayelet
authors.initials: A
authors.lastname: Harari
authors.affiliation: The Bert W. Strassburger Lipid Center, Sheba Medical Center, Tel-Hashomer 5265601, Israel. tal.almog@sheba.health.gov.il.
authors.forename: Tal
authors.initials: T
authors.lastname: Almog
authors.affiliation: The Bert W. Strassburger Lipid Center, Sheba Medical Center, Tel-Hashomer 5265601, Israel. Yehuda.Kamari@sheba.health.gov.il.|Sackler School of Medicine, Tel-Aviv University, Tel Aviv 6997801, Israel. Yehuda.Kamari@sheba.health.gov.il.
authors.forename: Yehuda
authors.initials: Y
authors.lastname: Kamari
authors.affiliation: N.B.T., Eilat 8810602, Israel. amiba@bezeqint.net.
authors.forename: Ami
authors.initials: A
authors.lastname: Ben-Amotz
authors.affiliation: The Bert W. Strassburger Lipid Center, Sheba Medical Center, Tel-Hashomer 5265601, Israel. Dror.Harats@sheba.health.gov.il.|Sackler School of Medicine, Tel-Aviv University, Tel Aviv 6997801, Israel. Dror.Harats@sheba.health.gov.il.
authors.forename: Dror
authors.initials: D
authors.lastname: Harats
authors.affiliation: The Bert W. Strassburger Lipid Center, Sheba Medical Center, Tel-Hashomer 5265601, Israel. aviv.shaish@sheba.health.gov.il.
authors.forename: Aviv
authors.initials: A
authors.lastname: Shaish
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1 / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001057:Apolipoproteins E / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D050197:Atherosclerosis / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002478:Cells, Cultured; D000460:Chlorophyta / Q000737:chemistry; D008076:Cholesterol, HDL / Q000097:blood / Q000378:metabolism*; D019587:Dietary Supplements; D004790:Enzyme Induction; D057847:Lipid Regulating Agents / Q000378:metabolism / Q000627:therapeutic use*; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010839:Phytoplankton / Q000737:chemistry; D000067996:RAW 264.7 Cells; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism; D000072516:Retinoic Acid 4-Hydroxylase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D019207:beta Carotene / Q000031:analogs & derivatives* / Q000378:metabolism / Q000627:therapeutic use
chemical_list: D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D001057:Apolipoproteins E; D008076:Cholesterol, HDL; D057847:Lipid Regulating Agents; D011973:Receptors, LDL; D000072516:Retinoic Acid 4-Hydroxylase; D019207:beta Carotene; C577833:Abca1 protein, mouse; C487540:ABCG1 protein, mouse; C000607081:Cyp26b1 protein, mouse
keywords: 9-cis-β-carotene; ATP Binding Cassette transporter A1; ATP Binding Cassette transporter G1; apolipoprotein E; cholesterol efflux; retinoic x receptor; reverse cholesterol transport