Polysaccharides and atherosclerosis: Focus on the role of key genes of cholesterol metabolism in macrophages

Based on nutrigenomics approaches, the mechanisms of action of glucan on the accumulation and efflux of cholesterol from macrophages derived from the THP-1 cell line were studied. At the first stage, it was established that glucan does not have the ability to inhibit the accumulation of Cholesterol in the macrophages caused by the action of modified low-density lipoproteins (mLDL) on them. However, glucan accelerates the efflux of Cholesterol from the macrophages loaded with it, and this effect is commensurate with the action of verapamil and alpinetin. At the second stage of the work, transcriptomic analysis made it possible to detect differentially expressed genes by observing the effect of glucan on both accumulation and efflux of Cholesterol from the macrophages. In mLDL-induced Cholesterol accumulation, the presence of glucan in the cell model did not change the overall pattern of gene expression, at the same time, monitoring Cholesterol efflux revealed the ability of glucan to increase (LDLR, INSIG1, SCARB1, STARD3, ABCA1) or decrease (FADS1, SR-BI, DSC1) the expression of a set of genes different from the key Cholesterol accumulation genes. Evaluation of the biological activity of genes, associated with accumulation Cholesterol, indicates their role in immune and inflammatory processes, while genes with other functions, including genes known as regulators of Cholesterol metabolism, are involved to a greater extent in & Scy;holesterol efflux under the action of glucan. A conclusion was made that in relation to the pathology of atherosclerosis, it is necessary to consider glucan not so much as a prophylactic, but as a therapeutic agent.