Epigenome-Wide Changes in the Cell Layers of the Vein Wall When Exposing the Venous Endothelium to Oscillatory Shear Stress

Epigenomes

article

Mariya A. Smetanina¹  Valeria A. Korolenya¹  Alexander E. Kel¹  Ksenia S. Sevostyanova⁵  Konstantin A. Gavrilov⁵  Andrey I. Shevela⁵  Maxim L. Filipenko¹ 

[1] Laboratory of Pharmacogenomics, Institute of Chemical Biology and Fundamental Medicine;Department of Fundamental Medicine, V. Zelman Institute for Medicine and Psychology, Novosibirsk State University;Department of Natural Sciences, Novosibirsk State University;Department of Research & Development;Center of New Medical Technologies, Institute of Chemical Biology and Fundamental Medicine;Laboratory of Invasive Medical Technologies, Institute of Chemical Biology and Fundamental Medicine;Department of Surgical Diseases, V. Zelman Institute for Medicine and Psychology, Novosibirsk State University

关键词: vein wall layers;    endothelial cells;    smooth muscle cells;    fibroblasts;    oscillatory shear stress;    DNA methylation;    gene regulation;    master regulators;   

DOI  :  10.3390/epigenomes7010008

学科分类：分子生物学，细胞生物学和基因

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY