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Updated: Apr 18, 2026
Isolation, Characterization, and Purification of Macrophages from Tissues Affected by Obesity-related Inflammation
Published on: April 3, 2017
The inhibition of macrophage foam cell formation by 9-cis β-carotene is driven by BCMO1 activity
Noa Zolberg Relevy1, Sapir Bechor1, Ayelet Harari2
1The Bert W. Strassburger Lipid Center, Sheba Medical Center, Tel-Hashomer, 5265601, Ramat-Gan, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
Insights
Dietary carotenoids like 9-cis beta-carotene inhibit foam cell formation, a key step in atherosclerosis. This occurs via conversion to retinoids in macrophages, activating nuclear receptors and reducing heart disease risk.
Area of Science:
- Cardiovascular Research
- Nutritional Science
- Cell Biology
Background:
- Atherosclerosis is a leading cause of death, driven by macrophage foam cell formation.
- Epidemiological studies link carotenoid-rich diets to reduced heart disease risk.
- Previous research showed Dunaliella algae inhibit atherogenesis in mice.
Purpose of the Study:
- Investigate if 9-cis beta-carotene inhibits macrophage foam cell formation.
- Determine if this effect is mediated by conversion to retinoids.
- Explore the role of beta-carotene 15,15'-monooxygenase (BCMO1) and RXR activation.
Main Methods:
- Utilized RAW264.7 macrophage cell line for in vitro studies.
- Administered Dunaliella algal powder to mice for in vivo experiments.
- Assayed for carotenoid accumulation, foam cell formation, BCMO1 activity, and RXR activation.
Main Results:
- 9-cis beta-carotene and Dunaliella extract inhibited foam cell formation in vitro.
- Dietary carotenoids accumulated in mouse peritoneal macrophages, inhibiting foam cell formation.
- BCMO1 was expressed and active in macrophages; 9-cis beta-carotene activated RXR.
Conclusions:
- Dietary 9-cis beta-carotene accumulates in macrophages and is converted to retinoids.
- Retinoids activate the nuclear receptor RXR, inhibiting foam cell formation.
- This mechanism highlights a dietary strategy to combat atherosclerosis.
Abstract:
Atherosclerosis is a major cause of morbidity and mortality in developed societies, and begins when activated endothelial cells recruit monocytes and T-cells from the bloodstream into the arterial wall. Macrophages that accumulate cholesterol and other fatty materials are transformed into foam cells. Several epidemiological studies have demonstrated that a diet rich in carotenoids is associated with a reduced risk of heart disease; while previous work in our laboratory has shown that the 9-cis β-carotene rich alga Dunaliella inhibits atherogenesis in mice. The effect of 9-cis β-carotene on macrophage foam cell formation has not yet been investigated. In the present work, we sought to study whether the 9-cis β-carotene isomer, isolated from the alga Dunaliella, can inhibit macrophage foam cell formation upon its conversion to retinoids. The 9-cis β-carotene and Dunaliella lipid extract inhibited foam cell formation in the RAW264.7 cell line, similar to 9-cis retinoic acid. Furthermore, dietary enrichment with the algal powder in mice resulted in carotenoid accumulation in the peritoneal macrophages and in the inhibition of foam cell formation ex-vivo and in-vivo. We also found that the β-carotene cleavage enzyme β-carotene 15,15'-monooxygenase (BCMO1) is expressed and active in macrophages. Finally, 9-cis β-carotene, as well as the Dunaliella extract, activated the nuclear receptor RXR in hepa1-6 cells. These results indicate that dietary carotenoids, such as 9-cis β-carotene, accumulate in macrophages and can be locally cleaved by endogenous BCMO1 to form 9-cis retinoic acid and other retinoids. Subsequently, these retinoids activate the nuclear receptor RXR that, along with additional nuclear receptors, can affect various metabolic pathways, including those involved in foam cell formation and atherosclerosis.
