Epigenetics and Vascular Senescence–Potential New Therapeutic Targets?

Ding, Qian; Shao, Chunhong; Rose, Peter; Zhu, Yi‐Zhun

doi:10.3389/fphar.2020.535395

Cited by 16 publications

(15 citation statements)

References 93 publications

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“…Growing evidences suggest that multiple non-coding RNAs are involved in regulating VSMC senescence (27), and are becoming master regulators of senescent signaling by finetune p53 activity (28,29). Unlike miRNAs directly targeting key proteins in p53 signaling pathway, circRNAs play their functional role through acting as miRNA and protein sponges or facilitating contact and assembly of proteins.…”

Section: Discussionmentioning

confidence: 99%

circ-Sirt1 Decelerates Senescence by Inhibiting p53 Activation in Vascular Smooth Muscle Cells, Ameliorating Neointima Formation

Kong

Dou

et al. 2021

Front. Cardiovasc. Med.

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Vascular smooth muscle cell (VSMC) senescence is a major driver of neointimal formation. We have demonstrated that circ-Sirt1 derived from the SIRT1 gene suppressed VSMC inflammation and neointimal formation. However, the effect of circ-Sirt1 inhibiting inflammation on VSMC senescence during neointimal hyperplasia remains to be elucidated. Here, we showed that circ-Sirt1 was highly expressed in young and healthy arteries, which was decreased in aged arteries and neointima of humans and mice. Overexpression of circ-Sirt1 delayed Ang II-induced VSMC senescence in vitro and ameliorated neointimal hyperplasia in vivo. Mechanically, circ-Sirt1 inhibited p53 activity at the levels of transcription and post-translation modulation. In detail, circ-Sirt1, on the one hand, interacted with and held p53 to block its nuclear translocation, and on the other hand, promoted SIRT1-mediated p53 deacetylation and inactivation. In conclusion, our data suggest that circ-Sirt1 is a novel p53 repressor in response senescence-inducing stimuli, and targeting circ-Sirt1 may be a promising approach to ameliorating aging-related vascular disease.

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Section: Discussionmentioning

confidence: 99%

circ-Sirt1 Decelerates Senescence by Inhibiting p53 Activation in Vascular Smooth Muscle Cells, Ameliorating Neointima Formation

Kong

Dou

et al. 2021

Front. Cardiovasc. Med.

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“…Aging is an inevitable process and significantly associated with many vascular aging-related disorders. Vascular aging is the structural and functional changes of the vasculature, including vascular cells senescence, inflammation, oxidative stress, and calcification ( Ding et al, 2020 ). With aging, there is a gradual increase in the prevalence and mortality of vascular aging-related diseases.…”

Section: Dna Methylation As a Diagnostic Tool And Therapeutic Target In Vascular Aging-related Diseasesmentioning

confidence: 99%

“…Vascular aging is characterized by gradual changes in the vasculature structure and function ( Laina et al, 2018 ; Ding et al, 2020 ). With aging, the structure and mechanical properties of vascular wall alter, i.e., lumen dilation, wall thickening, decreased arterial compliance, and increased arterial stiffness ( North and Sinclair, 2012 ).…”

Section: Introductionmentioning

confidence: 99%

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

Liu

2021

Front. Cell Dev. Biol.

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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.

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“…70 As is well known, the DNA methylation is regulated by a family of DNA methyltransferases, including DNMT1, DNMT3a, and DNMT3b. 70 In summary, the abnormal DNA methylation emerges in aged cells and accelerates the process of age-related diseases. DNA methylation, oxidative stress, and vascular senescence have a close relationship in blood vessels.…”

Section: Dna Methylationmentioning

confidence: 99%

The mechanisms of vascular aging

Wang

Mao

2021

Aging Medicine

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Vascular senescence is one of the hotspots in current research. With global average life expectancy increasing, delaying or reducing aging and age‐related diseases has become a pressing issue for improving quality of life. Vascular senescence is an independent risk factor for age‐related cardiovascular diseases (CVD) and results in the deterioration of CVD. Nevertheless, the underlying mechanisms of the vascular senescence have not been expressly illustrated. In this review, we attempt to summarize the recent literature in the field and discuss the major mechanisms involved in vascular senescence. We also underline key molecular aspects of aging‐associated vascular dysfunction in the attempt to highlight potential innovative therapeutic targets to delay the onset of age‐related diseases.

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Epigenetics and Vascular Senescence–Potential New Therapeutic Targets?

Cited by 16 publications

References 93 publications

circ-Sirt1 Decelerates Senescence by Inhibiting p53 Activation in Vascular Smooth Muscle Cells, Ameliorating Neointima Formation

circ-Sirt1 Decelerates Senescence by Inhibiting p53 Activation in Vascular Smooth Muscle Cells, Ameliorating Neointima Formation

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

The mechanisms of vascular aging

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