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• W3123399425 endingPage "100003" @default.
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• W3123399425 abstract "• Probucol is unable to completely inhibit cholesterol efflux in foam cells. • Functional nHDL is released from foam cells in the presence of probucol. • ABCA1 expression is the same in non-foam and foam cells, but with different efflux. • In probucol pretreated foam cells a new mechanism exists that is ABCA1-independent. Probucol is a cholesterol-lowering agent whose ability to prevent atherosclerosis is currently under study. Herein, we investigate the putative mechanism of probucol by observation of changes in cellular cholesterol efflux and lipid droplet morphology in macrophages. The inhibitory activity of probucol was assessed in non-foam or foam cell macrophages expressing ABCA1 generated by treatment with fetal calf serum (FCS) alone or in combination with acetylated LDL, respectively. Probucol inhibited cholesterol efflux to apolipoprotein A-I (apoA-I) by 31.5±0.1% in THP-1 non-foam cells and by 18.5±0.2% in foam cells. In probucol-treated non-foam THP-1 cells, nascent high density lipoprotein (nHDL) particles with a diameter < 7 nm were generated, while in probucol-treated THP-1 foam cells nHDL particles of > 7 nm in diameter containing cholesterol were produced. Foam cells also displayed a significant accumulation of free cholesterol at the plasma membrane, as measured by percent cholestenone formed. Intracellularly, there was a significant decrease in lipid droplet number and an increase in size in probucol-treated THP-1 foam cells when compared to non-treated cells. We report for the first time that probucol is unable to completely inhibit cholesterol efflux in foam cells to the same extent as in non-foam cells. Indeed, functional nHDL is released from foam cells in the presence of probucol. This difference in inhibitory effect could potentially be explained by changes in the plasma membrane pool as well as intracellular cholesterol storage independently of ABCA1." @default.
• W3123399425 created "2021-02-01" @default.
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• W3123399425 date "2021-01-01" @default.
• W3123399425 modified "2023-09-28" @default.
• W3123399425 title "Probucol treatment is associated with an ABCA1-independent mechanism of cholesterol efflux to lipid poor apolipoproteins from foam cell macrophages" @default.
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• W3123399425 doi "https://doi.org/10.1016/j.bbadva.2021.100003" @default.
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