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- W3174826720 abstract "Vitamin E can modulate the CD36/FAT scavenger receptor/fatty acids transporter activity and affect lipid accumulation in monocytes and macrophages, important events for inflammation, lipotoxicity and foam cells formation during atherosclerosis. Similar to that, cyclodextrins (CD) can sequester and trigger export of lipids and influence cholesterol-mediated signaling and gene expression leading to macrophages reprogramming and lipid lowering effects in a number of disease models. We have now combined the phosphorylated vitamin E analogue (alpha-tocopheryl phosphate, αTP) and beta-cyclodextrin (βCD) in a novel formulation to evaluate its regulatory effects and mechanisms of action on lipid accumulation in human monocytes/macrophages. In human THP-1 monocytes and macrophages, the αTP/βCD complex not only increased the cellular delivery of αTP, but also reduced lipid accumulation by reducing CD36/FAT surface exposition and/or by enhancing the removal of cholesterol from the cells/membranes. A comparable activity was observed with higher order complexes of αTP/βCD with three types of modified starches or chitosan that may be useful as protective vehicle to increase oral, dermal or ocular delivery, or act as deposit-enhancer in mucosa for delivery across epithelia. Moreover, preliminary results suggest that the αTP/βCD complex can influence signal transduction and gene expression pathways centrally involved in regulating cellular lipid homeostasis and inflammation. Thus, by acting as a Dual Action Lipid-lowering Complex (DALC), αTP/βCD may not only increase the delivery of αTP and reduce cellular lipid accumulation by influencing CD36-mediated signaling and gene expression relevant for lipid homeostasis, inflammation and cellular senescence, but also by stimulating βCD-mediated lipid removal and macrophage reprogramming. In vivo, similar or better reductions of cellular lipids/cholesterol may be achieved possibly at lower concentrations as result of increased bioavailability and stability of αTP and of enhanced βCD-mediated lipid exchange and macrophages reprogramming relevant not only for inflammation and atherosclerosis, but also for non-alcoholic steatohepatitis (NASH), tumorigenesis and Parkinson's Disease. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal." @default.
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- W3174826720 date "2019-04-01" @default.
- W3174826720 modified "2023-09-23" @default.
- W3174826720 title "Modulation of lipid accumulation in monocytes and macrophages by cyclodextrin‐based nanocarriers for alpha‐tocopheryl phosphate" @default.
- W3174826720 doi "https://doi.org/10.1096/fasebj.2019.33.1_supplement.654.14" @default.
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