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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 vasc...
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... evidence suggested that DNA methylation plays a significant role in regulating ECs, VSMCs, fibroblasts, and macrophages functions, and is implicated in the process of vascular aging and related disorders. Recent studies have identified a series of genes regulated through DNA methylation in the initiation and development of vascular aging ( Table 1). This section primarily focuses on the mechanisms and roles of DNA methylation in the functions of ECs and VSMCs (Figure 2). ...Similar publications
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...
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... DNA methylation is an important regulator of gene expression in vascular senescence (Ding et al., 2020;Xu et al., 2021). Environmental signals influence the activity of DNA methyltransferases (DNMT1) 1, 3a, and 3b (Denis et al., 2011). ...
... SAHF are domains of facultative heterochromatin in senescent cells that repress the expression of genes related to proliferation and are another biomarker of cellular senescence (Aird and Zhang, 2013). Abnormal DNA methylation patterns, prevalent in aging cells, have been widely associated with various age-related vascular diseases, hence their importance in vascular senescence (Tabaei and Tabaee, 2019;Xu et al., 2021). ...
Vascular diseases pose major health challenges, and understanding their underlying molecular mechanisms is essential to advance therapeutic interventions. Cellular senescence, a hallmark of aging, is a cellular state characterized by cell-cycle arrest, a senescence-associated secretory phenotype macromolecular damage, and metabolic dysregulation. Vascular senescence has been demonstrated to play a key role in different vascular diseases, such as atherosclerosis, peripheral arterial disease, hypertension, stroke, diabetes, chronic venous disease, and venous ulcers. Even though cellular senescence was first described in 1961, significant gaps persist in comprehending the epigenetic mechanisms driving vascular senescence and its subsequent inflammatory response. Through a comprehensive analysis, we aim to elucidate these knowledge gaps by exploring the network of epigenetic alterations that contribute to vascular senescence. In addition, we describe the consequent inflammatory cascades triggered by these epigenetic modifications. Finally, we explore translational applications involving biomarkers of vascular senescence and the emerging field of senotherapy targeting this biological process.
... Vascular aging is an independent risk factor for age-related diseases and a specific type of organic aging that affects the threshold, course, and severity of various CVD [2]. The process of vascular aging is marked by progressive alterations in vascular structure and function, primarily manifested through medial intima thickening, increased fibrosis, and decreased endothelial function [3][4][5][6]. ...
Vascular aging is an independent risk factor for age-related diseases and a specific type of organic aging. Endothelial progenitor cells (EPCs), a type of bone marrow stem cell, has been linked to vascular aging. The purpose of this study is to investigate if Ginseng-Sanqi-Chuanxiong (GSC) extract, a traditional Chinese medicine, can delay aortic aging in mice by enhancing the performance and aging of EPCs in vivo and to analyze the potential mechanisms through a d-Galactose (D-gal)-induced vascular aging model in mice. Our study revealed that GSC extracts not only enhanced the aortic structure, endothelial function, oxidative stress levels, and aging in mice, but also enhanced the proliferation, migration, adhesion, and secretion of EPCs in vivo, while reducing the expression of p53, p21, and p16. To conclude, GSC can delay vascular senescence by enhancing the function and aging of EPCs, which could be linked to a decrease in p16 and p53/p21 signaling. Consequently, utilizing GSC extracts to enhance the function and senescence of autologous EPCs may present a novel avenue for enhancing autologous stem cells in alleviating senescence.
... Accumulating evidence underscores the significant contribution of DNA methylation in the intricate orchestration of endothelial cells (EC), vascular smooth muscle cells (VSMC), fibroblasts, and macrophages' functionalities [16]. This epigenetic mechanism plays an important role not only in the individual functions of these cell types but also in the coordination of their interactions within the vascular. ...
... Moreover, DNA methylation's involvement extends beyond cellular function, including critical processes associated with vascular aging and a spectrum of related diseases. Within this dynamic context, DNA methylation acts as a regulatory switch, influencing gene expression patterns that steer the behavior of ECs, VSMCs, fibroblasts, and macrophages [16]. These distinct cellular entities collectively shape the vascular microenvironment, playing roles in processes such as angiogenesis, vascular tone regulation, extracellular matrix maintenance, and immune responses [16]. ...
... Within this dynamic context, DNA methylation acts as a regulatory switch, influencing gene expression patterns that steer the behavior of ECs, VSMCs, fibroblasts, and macrophages [16]. These distinct cellular entities collectively shape the vascular microenvironment, playing roles in processes such as angiogenesis, vascular tone regulation, extracellular matrix maintenance, and immune responses [16]. ...
In an era of rapid technological advancement, a notable and convincing demographic trend is emerging: a significant increase in the elderly population. This demographic shift is represented by numerous factors, including enhanced healthcare, medical breakthroughs, and improved living standard conditions. This transformation brings numerous concerns for the health and well-being of the elderly. This concern is particularly pronounced when considering the impact of cardiovascular aging, a critical facet of their overall health that carries substantial implications for governments and healthcare systems worldwide. However, people’s knowledge of these diseases and our ability to control epidemics is still limited. Cardiovascular aging brings many changes to our lives and poses high risks for the elderly. This report aims to analyze cardiovascular changes and combine existing medical methods to make efficient suggestions. To address the challenges posed by the aging population to cardiovascular disease, it is important to cultivate a comprehensive approach that includes risk factor management, lifestyle interventions, and advanced therapies.
... A previous study demonstrated alcohol consumption enhances blood pressure through inhibition of endothelial nitric oxide synthase and promotion of oxidative injury to the endothelium [21]. DNAm at gene promoter regions, catalyzed by DNA methyl transferases, may stimulate proliferation and inflammation in endothelial cells [39]. In addition, ROS in aging endothelial cells may reinforce this DNAmrelated damage [40]. ...
The alcohol-associated biological aging remains to be studied across adulthood. We conducted linear regression analyses to investigate the associations between alcohol consumption and two DNA methylation-based biological age acceleration metrics in 3823 Framingham Heart Study participants (24-92 years and 53.8% women) adjusting for covariates. We also investigated whether the two epigenetic aging metrics mediated the association of alcohol consumption with hypertension. We found that higher long-term average alcohol consumption was significantly associated with biological age acceleration assessed by GrimAge acceleration (GAA) and PhenoAge acceleration (PAA) in middle-aged (45-64 years, n = 1866) and older (65-92 years, n = 1267) participants while not in young participants (24-44 years, n = 690). For example, one additional standard drink of alcohol (~14 grams of ethanol per day) was associated with a 0.71 ± 0.15-year (p = 2.1e-6) and 0.60 ± 0.18-year (p = 7.5e-4) increase in PAA in middle-aged and older participants, respectively, but the association was not significant in young participants (p = 0.23). One additional standard serving of liquor (~14 grams of ethanol) was associated with a greater increase in GAA (0.82-year, p = 4.8e-4) and PAA (1.45-year, p = 7.4e-5) than beer (GAA: 0.45-year, p = 5.2e-4; PAA: 0.48-year, p = 0.02) and wine (GAA: 0.51-year, p = 0.02; PAA: 0.91-year, p = 0.008) in middle-aged participant group. We observed that up to 28% of the association between alcohol consumption and hypertension was mediated by GAA or PAA in the pooled sample. Our findings suggest that alcohol consumption is associated with greater biological aging quantified by epigenetic aging metrics, which may mediate the association of alcohol consumption with quantitative traits, such as hypertension.
... Epigenetic factors regulate changes in cellular functions and thus affect EC senescence. DNA methylation is an epigenetic mechanism that is regulated by a combination of methyltransferases and demethylases, and a central role for DNA methylation in vascular senescence-related diseases has been identified [60]. Ramini et al. analyzed genome-wide DNA methylation in normal and senescent HUVECs and noted a significant increase in demethylated sequences in senescent cells [61]. ...
Endothelial cells, which are highly dynamic cells essential to the vascular network, play an indispensable role in maintaining the normal function of the body. Several lines of evidence indicate that the phenotype associated with senescent endothelial cells causes or promotes some neurological disorders. In this review, we first discuss the phenotypic changes associated with endothelial cell senescence; subsequently, we provide an overview of the molecular mechanisms of endothelial cell senescence and its relationship with neurological disorders. For refractory neurological diseases such as stroke and atherosclerosis, we intend to provide some valid clues and new directions for clinical treatment options.
... Those specific CpG sites were very close to the transcription starting site (TSS) of the gene promoters, strongly indicating a link to increased Agtr1a and Prkcb gene expression, as well as AT1R and PKCβ protein levels in the MHF-MA group. A number of previous studies have also shown that if specific CpG sites at the transcription starting site of gene promoters were hypo-methylated, corresponding gene expression could be affected [28]. Therefore, our study found that hypo-methylation mediated Agtr1a and Prkcb gene expression may contribute to the abnormal axis and hyper-vasoconstriction in MHF offspring. ...
Perinatal malnutrition affects vascular functions, and calcium is important in vascular regulations. It is unknown whether and how perinatal maternal high-fat diets (MHF)-mediated vascular dysfunction occurs via the angiotensin-PKC-L-type-calcium-channels (LTCC) axis. This study determined angiotensin II (AII) roles in the PKC-LTCC axis in controlling calcium influx in the arteries of offspring after perinatal MHF. Mesenteric arteries (MA) and smooth muscle cells (SMCs) from 5-month-old offspring rats were studied using physiological, ion channel, molecular, and epigenetic analysis. Pressor responses to AII were significantly increased in the free-moving MHF offspring rats. In cell experiments, MA-SMC proliferation was enhanced, and associated with thicker vascular wall in the obese offspring. Imaging analysis showed increase of fluorescence Ca2+ intensity in the SMCs of the MHF group. Angiotensin II receptor (AT1R)-mediated PKC-LTCC axis in vasoconstrictions was altered by perinatal MHF via reduced DNA methylation at specific CpG sites of Agtr1a and Prkcb gene promoters at the transcription level. Accordingly, mRNA and protein expression of AT1R and PKCβ in the offspring MA were increased, contributing to enhanced Ca2+ currents and vascular tone. The results showed that DNA methylation resulted in perinatal MHF-induced vascular disorders via altered AT1-PKC-LTCC pathway in resistance arteries of the offspring, providing new insights into the pathogenesis and early prevention/treatments for hypertension in developmental origins.
... The involvement of vessel wall mechanics and hemodynamics in atherosclerosis has been amply demonstrated (30). The vascular intimal layer, which is composed of endothelial cells, an internal elastic layer and fibrous collagen tissue, plays a key role in preventing platelet aggregation and antithrombosis (31,32). Disruption of the endothelium is a key factor in the initial development of atherosclerotic disease within the vessel wall (33). ...
Chronic internal carotid artery occlusion (CICAO) has high prevalence and incidence rates, and patients with CICAO can be completely asymptomatic, experience a devastating stroke or die. It is important to note that CICAO causes cerebrovascular accidents. Currently, the external carotid-internal carotid (EC-IC) bypass technique is used to treat CICAO. However, many clinical studies showed that EC-IC bypass was not beneficial for many patients with CICAO. Meanwhile, endovascular intervention treatment options for CICAO are evolving, and an increasing number of patients are undergoing endovascular intervention therapy. Accordingly, a review comparing both techniques is warranted. For this review, we searched PubMed and collected relevant case study reports comparing endovascular interventional therapy and internal and external cervical bypass surgeries to provide strategies for clinical treatment.
... Many age-related vascular diseases are due to the aging-induced functional and phenotypic alterations of the microcirculation [2]. Accumulating evidence indicated that vascular aging is a major trigger of many vascular disorders and enhances the incidence and mortality of atherosclerosis [9], hypertension [10], cerebral small vessel disease [11], Alzheimer's disease [12], stroke [11], etc. Vascular aging is a specific type of organic aging characterized by structural and functional alterations in the vasculature, including vascular cell senescence, extracellular matrix (ECM) remodeling, oxidative stress, inflammation, apoptosis, and calcification, which are implicated in the development and progression of vascular aging-related diseases [13]. Vascular aging and vascular diseases interact with each other. ...
Vascular aging is a specific type of organic aging that plays a central role in the morbidity and mortality of cardiovascular and cerebrovascular diseases among the elderly. It is essential to develop novel interventions to prevent/delay age-related vascular pathologies by targeting fundamental cellular and molecular aging processes. Endogenous vasoactive peptides are compounds formed by a group of amino acids connected by peptide chains that exert regulatory roles in intercellular interactions involved in a variety of biological and pathological processes. Emerging evidence suggests that a variety of vasoactive peptides play important roles in the occurrence and development of vascular aging and related diseases such as atherosclerosis, hypertension, vascular calcification, abdominal aortic aneurysms, and stroke. This review will summarize the cumulative roles and mechanisms of several important endogenous vasoactive peptides in vascular aging and vascular aging-related diseases. In addition, we also aim to explore the promising diagnostic function as biomarkers and the potential therapeutic application of endogenous vasoactive peptides in vascular aging-related diseases.
... All three epigenetic mechanisms are well documented in vascular biology. DNA methylation changes have been demonstrated in homocysteine-induced atherosclerosis [101], VSMc proliferation and migration which leads to intimal hyperplasia and restenosis [102], flow-dependent atherosclerosis [103], and vascular calcification [17,102,104]. ...
Lower extremity artery disease (LEAD), caused by atherosclerotic obstruction of the arteries of the lower limb extremities, has exhibited an increase in mortality and morbidity worldwide. The phenotypic variability of LEAD is correlated with its complex, multifactorial etiology. In addition to traditional risk factors, it has been shown that the interaction between genetic factors (epistasis) or between genes and the environment potentially have an independent role in the development and progression of LEAD. In recent years, progress has been made in identifying genetic variants associated with LEAD, by Genome-Wide Association Studies (GWAS), Whole Exome Sequencing (WES) studies, and epigenetic profiling. The aim of this review is to present the current knowledge about the genetic factors involved in the etiopathogenic mechanisms of LEAD, as well as possible directions for future research. We analyzed data from the literature, starting with candidate gene-based association studies, and then continuing with extensive association studies, such as GWAS and WES. The results of these studies showed that the genetic architecture of LEAD is extremely heterogeneous. In the future, the identification of new genetic factors will allow for the development of targeted molecular therapies, and the use of polygenic risk scores (PRS) to identify individuals at an increased risk of LEAD will allow for early prophylactic measures and personalized therapy to improve their prognosis.
... DNA methylation induces changes in gene expression without changing the DNA sequence by adding methyl groups to cytosine in a CpG-containing nucleotide to form 5-methylcytosine. [1,2] DNA methylation is a dynamically reversible process regulated by methyltransferases and demethyltransferases. [3] Currently, DNA methyltransferase inhibitors are recommended for clinical use in various cancers such as myelodysplastic syndromes and chronic myelomonocytic leukemia. [4] DNA methyltransferase inhibitors, including decitabine, azacytidine, and RG108, can reverse atherosclerosis, diabetes, and cardiac hypertrophy [5][6][7] ; however, they have not been used clinically against cardiovascular diseases (CVDs). ...
... Keywords with strong explosive power are another important index reflecting research frontiers and hotspots (Fig. 7). The citation burst time of keywords including "epigenome wide association" (2016-2021), [42] "long non-coding RNA" (2017-2021), "population" (2017-2021), "metabolism" (2017-2021), [43] "biomarker" (2019-2021), [44] "protein" (2019-2021), "age" (2019-2021), [3] and "cardiovascular risk" (2019-2021) [45] have continued to 2021, and the burst is still ongoing, indicating that these research contents have received great attention in recent years and may become new research frontiers in the future. ...
Background:
DNA methylation is a dynamically reversible form of epigenetics. Dynamic regulation plays an important role in cardiovascular diseases (CVDs). However, there have been few bibliometric studies in this field. We aimed to visualize the research results and hotspots of DNA methylation in CVDs using a bibliometric analysis to provide a scientific direction for future research.
Methods:
Publications related to DNA methylation in CVDs from January 1, 2001, to September 15, 2021, were searched and confirmed from the Web of Science Core Collection. CiteSpace 5.7 and VOSviewer 1.6.15 were used for bibliometric and knowledge-map analyses.
Results:
A total of 2617 publications were included in 912 academic journals by 15,584 authors from 963 institutions from 85 countries/regions. Among them, the United States of America, China, and England were the top 3 countries contributing to the field of DNA methylation. Harvard University, Columbia University, and University of Cambridge were the top 3 contributing institutions in terms of publications and were closely linked. PLoS One was the most published and co-cited journal. Baccarelli Andrea A published the most content, while Barker DJP had the highest frequency of co-citations. The keyword cluster focused on the mechanism, methyl-containing substance, exposure/risk factor, and biomarker. In terms of research hotspots, references with strong bursts, which are still ongoing, recently included "epigenetic clock" (2017-2021), "obesity, smoking, aging, and DNA methylation" (2017-2021), and "biomarker and epigenome-wide association study" (2019-2021).
Conclusions:
We used bibliometric and visual methods to identify research hotspots and trends in DNA methylation in CVDs. Epigenetic clocks, biomarkers, environmental exposure, and lifestyle may become the focus and frontier of future research.
