1. 9-cis β-Carotene Increased Cholesterol Efflux to HDL in Macrophages.
- Author
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Bechor S, Zolberg Relevy N, Harari A, Almog T, Kamari Y, Ben-Amotz A, Harats D, and Shaish A
- Subjects
- ATP Binding Cassette Transporter 1 agonists, ATP Binding Cassette Transporter 1 genetics, ATP Binding Cassette Transporter 1 metabolism, ATP Binding Cassette Transporter, Subfamily G, Member 1 agonists, ATP Binding Cassette Transporter, Subfamily G, Member 1 genetics, ATP Binding Cassette Transporter, Subfamily G, Member 1 metabolism, Animals, Apolipoproteins E agonists, Apolipoproteins E genetics, Apolipoproteins E metabolism, Atherosclerosis immunology, Atherosclerosis metabolism, Atherosclerosis pathology, Cells, Cultured, Chlorophyta chemistry, Cholesterol, HDL blood, Enzyme Induction, Lipid Regulating Agents metabolism, Macrophages, Peritoneal immunology, Macrophages, Peritoneal pathology, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Phytoplankton chemistry, RAW 264.7 Cells, Receptors, LDL genetics, Receptors, LDL metabolism, Retinoic Acid 4-Hydroxylase chemistry, Retinoic Acid 4-Hydroxylase genetics, Retinoic Acid 4-Hydroxylase metabolism, beta Carotene metabolism, beta Carotene therapeutic use, Atherosclerosis prevention & control, Cholesterol, HDL metabolism, Dietary Supplements, Lipid Regulating Agents therapeutic use, Macrophages, Peritoneal metabolism, Up-Regulation, beta Carotene analogs & derivatives
- 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.
- Published
- 2016
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