| Autor: |
Smetanina MA; Laboratory of Pharmacogenomics, Institute of Chemical Biology and Fundamental Medicine (ICBFM) SB RAS, Novosibirsk 630090, Russia.; Department of Fundamental Medicine, V. Zelman Institute for Medicine and Psychology, Novosibirsk State University (NSU), Novosibirsk 630090, Russia., Korolenya VA; Laboratory of Pharmacogenomics, Institute of Chemical Biology and Fundamental Medicine (ICBFM) SB RAS, Novosibirsk 630090, Russia.; Department of Natural Sciences, Novosibirsk State University (NSU), Novosibirsk 630090, Russia., Kel AE; Laboratory of Pharmacogenomics, Institute of Chemical Biology and Fundamental Medicine (ICBFM) SB RAS, Novosibirsk 630090, Russia.; Department of Research & Development, GeneXplain GmbH, D-38302 Wolfenbüttel, Germany., Sevostyanova KS; Center of New Medical Technologies, Institute of Chemical Biology and Fundamental Medicine (ICBFM) SB RAS, Novosibirsk 630090, Russia.; Laboratory of Invasive Medical Technologies, Institute of Chemical Biology and Fundamental Medicine (ICBFM) SB RAS, Novosibirsk 630090, Russia.; Department of Surgical Diseases, V. Zelman Institute for Medicine and Psychology, Novosibirsk State University (NSU), Novosibirsk 630090, Russia., Gavrilov KA; Center of New Medical Technologies, Institute of Chemical Biology and Fundamental Medicine (ICBFM) SB RAS, Novosibirsk 630090, Russia.; Department of Surgical Diseases, V. Zelman Institute for Medicine and Psychology, Novosibirsk State University (NSU), Novosibirsk 630090, Russia., Shevela AI; Center of New Medical Technologies, Institute of Chemical Biology and Fundamental Medicine (ICBFM) SB RAS, Novosibirsk 630090, Russia.; Laboratory of Invasive Medical Technologies, Institute of Chemical Biology and Fundamental Medicine (ICBFM) SB RAS, Novosibirsk 630090, Russia.; Department of Surgical Diseases, V. Zelman Institute for Medicine and Psychology, Novosibirsk State University (NSU), Novosibirsk 630090, Russia., Filipenko ML; Laboratory of Pharmacogenomics, Institute of Chemical Biology and Fundamental Medicine (ICBFM) SB RAS, Novosibirsk 630090, Russia. |
| Abstrakt: |
Epigenomic changes in the venous cells exerted by oscillatory shear stress towards the endothelium may result in consolidation of gene expression alterations upon vein wall remodeling during varicose transformation. We aimed to reveal such epigenome-wide methylation changes. Primary culture cells were obtained from non-varicose vein segments left after surgery of 3 patients by growing the cells in selective media after magnetic immunosorting. Endothelial cells were either exposed to oscillatory shear stress or left at the static condition. Then, other cell types were treated with preconditioned media from the adjacent layer's cells. DNA isolated from the harvested cells was subjected to epigenome-wide study using Illumina microarrays followed by data analysis with GenomeStudio (Illumina), Excel (Microsoft), and Genome Enhancer (geneXplain) software packages. Differential (hypo-/hyper-) methylation was revealed for each cell layer's DNA. The most targetable master regulators controlling the activity of certain transcription factors regulating the genes near the differentially methylated sites appeared to be the following: (1) HGS, PDGFB, and AR for endothelial cells; (2) HGS, CDH2, SPRY2, SMAD2, ZFYVE9, and P2RY1 for smooth muscle cells; and (3) WWOX, F8, IGF2R, NFKB1, RELA, SOCS1, and FXN for fibroblasts. Some of the identified master regulators may serve as promising druggable targets for treating varicose veins in the future. |
