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Open AccessArticle

9-cis β-Carotene Increased Cholesterol Efflux to HDL in Macrophages

1
The Bert W. Strassburger Lipid Center, Sheba Medical Center, Tel-Hashomer 5265601, Israel
2
Sackler School of Medicine, Tel-Aviv University, Tel Aviv 6997801, Israel
3
N.B.T., Eilat 8810602, Israel
*
Author to whom correspondence should be addressed.
Nutrients 2016, 8(7), 435; https://doi.org/10.3390/nu8070435
Received: 19 March 2016 / Revised: 29 May 2016 / Accepted: 14 July 2016 / Published: 19 July 2016
(This article belongs to the Special Issue Vitamin A Update 2016)
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. View Full-Text
Keywords: 9-cis-β-carotene; reverse cholesterol transport; cholesterol efflux; ATP Binding Cassette transporter A1; ATP Binding Cassette transporter G1; apolipoprotein E; retinoic x receptor 9-cis-β-carotene; reverse cholesterol transport; cholesterol efflux; ATP Binding Cassette transporter A1; ATP Binding Cassette transporter G1; apolipoprotein E; retinoic x receptor
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Bechor, S.; Zolberg Relevy, N.; Harari, A.; Almog, T.; Kamari, Y.; Ben-Amotz, A.; Harats, D.; Shaish, A. 9-cis β-Carotene Increased Cholesterol Efflux to HDL in Macrophages. Nutrients 2016, 8, 435.

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