DNA methylation abnormalities in atherosclerosis

Abstract

Atherosclerosis is a complex disease with involvement of intermediate-, large-sized arteries. Atherosclerosis is characterized by the accumulation of vascular lipids, immune system activation, inflammation, oxidative stress and oxidized low-density lipoproteins (LDLs), endothelial cell (EC) activation, arterial smooth muscle cell (SMC) proliferation, macrophage activation and foam cell formation that cause endothelial dysfunction. DNA methylation is one of important epigenetic mechanisms which changes gene expression. It has been evident that this mechanism plays an important role in the initiation and propagation of atherosclerosis. Furthermore, DNA methylation is a crucial and distinct mechanism that modulates genes governing cell proliferation, thereby connecting environmental insults with gene expression. This study represents many atherosclerosis-related genes which are regulated through DNA methylation mechanism. Although the role of epigenetics in atherosclerosis is at their infancy. Nevertheless, various studies demonstrated that DNA methylation involvement in this disease is undeniable. DNA methyltransferases are the main player of the smooth muscle cell proliferation, endothelial cell integrity, as well as arteriosclerosis formation. In this review, we focus on recent achievements in the functional and description interpretation of the DNA methylation pattern of cells and tissues implicated in atherosclerosis. Besides, we discuss the association of DNA methylation with oxidative stress, hyperhomocysteinemia (HHcy), ageing, and inflammation in the development and pathogenesis of atherosclerosis.

Unveiling ncRNA regulatory axes in atherosclerosis progression

“…Thus, there is an urgent need to develop a more personalized medicine, and to enhance patient care through improved diagnostic sensitivity with more effective interventions in ATH prevention and treatment [4]. In this sense, years of research on the genomic basis of ATH have provided the biomedical community with a knowledge of gene‐related ATH risk factors, such as SNPs [5,6], genes and gene variants [7–9], alterations in DNA methylation [10,11], changes in gene expression [12,13], etc. Nevertheless, in the last years a new player has entered the game of disease‐associated genes: the highly heterogeneous group of non‐coding RNAs, which are progressively becoming important factors for atherosclerosis (and other diseases) research either as biomarkers of disease progression or as pathophysiological intermediates, while their operative interactions highlight the remarkable structural and functional complexity of the human genome.…”

Incretin drugs effect on epigenetic machinery: New potential therapeutic implications in preventing vascular diabetic complications

“…2,3 To these regards, DNA methylation, the most well-established epigenetic mark, has been shown to regulate the expression of genes involved in vascular biology playing an important role in vascular dysfunction and atherosclerosis development and progression. 4 DNA methylation is a dynamic process in which methylation could be synthesized "de novo", maintained or removed. DNA methyltransferases (DNMTs) and DNA demethylases maintain this process with an intricate balance.…”

Histone Demethylase JMJD3 Mediated Doxorubicin-Induced Cardiomyopathy by Suppressing SESN2 Expression

“…Decreased H3K27me3 level at the promoter region always associated with transcriptional activation ( Papait et al, 2020 ). However, changes of histone methylation not always strictly determine the transcriptional inhibition or activation of different target genes ( Wang et al, 2016 ; Jasiulionis, 2018 ; Tabaei and Tabaee, 2019 ). One methyltransferase or demethylase may act as epigenetic silencer or activator at the same time ( Wang et al, 2016 ).…”