Poster Topical Area: Vitamins and Minerals
Location: Hall D
Poster Board Number: 541
Objectives: The modulation of the CD36/FAT scavenger receptor/fatty acids transporter activity by micronutrients and vitamin E influences signaling and gene expression and reduces lipid accumulation in monocytes and macrophages, important events for inflammation 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, aTP) and CD in a novel formulation and tested its regulatory effects on lipid accumulation in human monocytes and macrophages.
Methods: CD36/FAT surface exposition, the uptake of fluorescent oxLDL and the accumulation of lipids were measured in human THP-1 monocytes by fluorescent activated cell sorting; lipid accumulation in THP-1 macrophages was determined by lipid staining with Oil Red O. Regulatory effects on signaling and gene expression of lipid homeostasis pathways were measured by luciferase reporter assays.
Results: The aTP/CD complex not only increased the cellular delivery of aTP, but also reduced oxLDL/lipids accumulation by reducing CD36/FAT surface exposition and/or by enhancing the removal of cholesterol from the cells/membranes. In addition, the aTP/CD complex influenced signal transduction and gene expression pathways centrally involved in regulating lipid homeostasis. A comparable activity was observed with higher order complexes of aTP/CD 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.
Conclusions: As a Dual Action Lipid-lowering Complex (DALC), aTP/CD increased the delivery of aTP and reduced cellular lipid accumulation by influencing signaling and gene expression relevant for lipid homeostasis and by stimulating CD-mediated lipid removal. 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 aTP and of enhanced lipid exchange and macrophages reprogramming.
University of Miami