ИСТИНА

The inflammatory processes in the endothelium may result in the development of cardiovascular diseases. Proinflammatory cytokines stimulate the expression of cell adhesion molecules on the surface of endothelial cells thus promoting adhesion and transmigration of leukocytes. It has been previously shown that the mitochondriatargeted compounds SkQ1, C12TPP, and DNP lowered the expression of endothelial proinflammatory cytokines and adhesion molecules including ICAM1. Noteworthy decreased expression of ICAM1 sustained for many days indicating the possible involvement of epigenetic modification(s) in the ICAM1 promoter. We hypothesized that the long-term effect of the studied compounds on ICAM1 mRNA expression could be achieved via the modulation of CpG methylation level of its promoter. The aim of our work was to study the effect of SkQ1, C12TPP and DNP on the methylation of the ICAM1 gene promoter. Our results indicate that both C12TPP and DNP increase CpG methylation in the ICAM1 promoter in EA.hy926 cells. This increase in the CpG methylation coincides with the decreased ICAM1 mRNA expression. The results suppose that the modulation of mitochondrial function in the endothelial cells leads to the epigenetic regulation of ICAM1 gene expression via CpG methylation of ICAM1 promotor. The study was supported by the RFBR grant No. 18-04-01110.