Roles and Mechanisms of DNA Methylation in Vascular Aging and Related Diseases

Abstract

Vascular aging is a pivotal risk factor promoting vascular dysfunction, the development and progression of vascular aging-related diseases. The structure and function of endothelial cells (ECs), vascular smooth muscle cells (VSMCs), fibroblasts, and macrophages are disrupted during the aging process, causing vascular cell senescence as well as vascular dysfunction. DNA methylation, an epigenetic mechanism, involves the alteration of gene transcription without changing the DNA sequence. It is a dynamically reversible process modulated by methyltransferases and demethyltransferases. Emerging evidence reveals that DNA methylation is implicated in the vascular aging process and plays a central role in regulating vascular aging-related diseases. In this review, we seek to clarify the mechanisms of DNA methylation in modulating ECs, VSMCs, fibroblasts, and macrophages functions and primarily focus on the connection between DNA methylation and vascular aging-related diseases. Therefore, we represent many vascular aging-related genes which are modulated by DNA methylation. Besides, we concentrate on the potential clinical application of DNA methylation to serve as a reliable diagnostic tool and DNA methylation-based therapeutic drugs for vascular aging-related diseases.

Analyzing Corin–BNP–NEP Protein Pathway Revealing Differential Mechanisms in AF-Related Ischemic Stroke and No AF-Related Ischemic Stroke

“…DNAm is involved in vascular aging and plays a central role in regulating age-related vascular diseases. Moreover, arterial stiffness and vascular aging trigger cerebrovascular dysfunction and constriction of the blood-brain barrier, leading to cerebrovascular diseases ( Thorin-Trescases et al, 2018 ; Xu et al, 2021 ). The evaluation of vascular aging might aid in stroke risk assessment in a community-based Chinese cohort conducted with 11,474 participants ( Yang et al, 2019 ).…”

“…Several studies demonstrated that DNAm regulates several cardiovascular and cerebrovascular diseases, such as cardiac remodeling, heart failure, atherosclerosis, stroke, dementia, and AD ( Chen et al, 2021 ; Xu et al, 2021 ). Recent studies have highlighted the critical role of mechanosensory-related epigenetics in local endothelial dysfunction and regional susceptibility to vascular disease.…”

Nanoparticles in the diagnosis and treatment of vascular aging and related diseases

“… 178 Epigenetics, including DNA/RNA methylation, histone modifications, microRNAs (miRNAs), and long non-coding RNAs (lncRNAs) exhibited a broad range of roles in vascular aging progression. 135 , 179 , 180 In mammals, DNA methylation involves the transfer of a methyl group to the C5 position of cytosine. DNA methylation recruited gene repression proteins or suppressed transcription factors bind DNA, thereby modulating gene expressions.…”

“… 181 During vascular aging, DNA methylation patterns within vascular cells are altered. 179 RNA methylation occurs in all stages of the RNA lifecycle, including RNA processing, nuclear export, translation regulation to RNA degradation, implying that it is an essential internal modification of RNA metabolism. It has been recognized that RNA methylation, especially N6-methyladenosine, shows a regulatory impact on DNA damage, immunity, cell growth, apoptosis, and aging.…”

Epigenetic Regulation in Pathology of Atherosclerosis: A Novel Perspective

“…Epigenetic “erasers” include ten-eleven translocation (TET) methylcytosine dioxygenases, histone deacetylases (HDACs). The coordination of epigenetic readers, writers, and erasers regulates gene expression either by active epigenetic marks or repressive epigenetic marks towards target gene promoters ( Xu et al, 2021b ). Non-coding RNA refers to RNA that cannot be translated into protein, and in the past, noncoding RNA was considered to be insignificant in gene transcription.…”