Epigenetic basis of diabetic vasculopathy

Bhamidipati, Theja; Kumar, Manishekhar; Verma, Sumit Singh; Mohanty, Sujit K.; Kaçar, Sedat; Reese, Diamond; Martínez, Michelle; Kamocka, Malgorzata M.; Dunn, Kenneth W.; Sen, Chandan K.; Singh, Kanhaiya

doi:10.3389/fendo.2022.989844

Cited by 14 publications

(7 citation statements)

References 159 publications

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“… 120 Fibroblasts of diabetic foot ulcer origin were identified as having sustained altered levels of DNA methylation even after prolonged passaging through normoglycemic conditions. 248 Hyperglycemia also promotes diabetic cardiac fibrosis by regulating DNA methylation levels. 249 5, 10 methylenetetrahydrofolate reductase (MTHFR) is a crucial regulatory enzyme in cardiac fibroblasts that modulates fibrosis and pyroptosis.…”

Section: Cells Involved In Metabolic Memorymentioning

confidence: 99%

Metabolic memory: mechanisms and diseases

Dong,

Sun,

Nie

et al. 2024

Sig Transduct Target Ther

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Metabolic diseases and their complications impose health and economic burdens worldwide. Evidence from past experimental studies and clinical trials suggests our body may have the ability to remember the past metabolic environment, such as hyperglycemia or hyperlipidemia, thus leading to chronic inflammatory disorders and other diseases even after the elimination of these metabolic environments. The long-term effects of that aberrant metabolism on the body have been summarized as metabolic memory and are found to assume a crucial role in states of health and disease. Multiple molecular mechanisms collectively participate in metabolic memory management, resulting in different cellular alterations as well as tissue and organ dysfunctions, culminating in disease progression and even affecting offspring. The elucidation and expansion of the concept of metabolic memory provides more comprehensive insight into pathogenic mechanisms underlying metabolic diseases and complications and promises to be a new target in disease detection and management. Here, we retrace the history of relevant research on metabolic memory and summarize its salient characteristics. We provide a detailed discussion of the mechanisms by which metabolic memory may be involved in disease development at molecular, cellular, and organ levels, with emphasis on the impact of epigenetic modulations. Finally, we present some of the pivotal findings arguing in favor of targeting metabolic memory to develop therapeutic strategies for metabolic diseases and provide the latest reflections on the consequences of metabolic memory as well as their implications for human health and diseases.

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Section: Cells Involved In Metabolic Memorymentioning

confidence: 99%

Metabolic memory: mechanisms and diseases

Dong,

Sun,

Nie

et al. 2024

Sig Transduct Target Ther

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“…Although current treatment strategies, including roux-en-Y gastric bypass surgery, can treat T2DM complicated with OSA (T2DM-OSA), the incidence of T2DM-OSA remains high owing to the increasing incidence of T2DM [ 4 , 5 ]. T2DM-OSA can cause peripheral vascular diseases due to blood-borne factors not reaching the affected tissues, and vascular endothelial dysfunction is common [ 6 , 7 ]. Long-term hyperglycaemia, inflammation, and oxidative stress are precursors of vascular endothelial cell injury in diabetes mellitus [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

LncRNA NEAT1 aggravates human microvascular endothelial cell injury by inhibiting the Apelin/Nrf2/HO-1 signalling pathway in type 2 diabetes mellitus with obstructive sleep apnoea

Chen,

Ou,

Huang

et al. 2024

Epigenetics

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Long noncoding RNAs (lncRNAs) regulate the progression of type 2 diabetes mellitus complicated with obstructive sleep apnoea (T2DM-OSA). However, the role of the lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) in T2DM-OSA remains unknown. This study aimed to reveal the function of NEAT1 in T2DM-OSA and the underlying mechanism. KKAy mice were exposed to intermittent hypoxia (IH) or intermittent normoxia to generate a T2DM-OSA mouse model. HMEC-1 cells were treated with high glucose (HG) and IH to construct a T2DM-OSA cell model. RNA expression was detected by qRT-PCR. The protein expression of Apelin, NF-E2-related factor 2 (Nrf2), haem oxygenase-1 (HO-1), and up-frameshift suppressor 1 (UPF1) was assessed using western blot. Cell injury was evaluated using flow cytometry, enzyme-linked immunosorbent assay, and oxidative stress kit assays. RIP, RNA pull-down, and actinomycin D assays were performed to determine the associations between NEAT1, UPF1, and Apelin. NEAT1 expression was upregulated in the aortic vascular tissues of mice with T2DM exposed to IH and HMEC-1 cells stimulated with HG and IH, whereas Apelin expression was downregulated. The absence of NEAT1 protected HMEC-1 cells from HG- and IH-induced damage. Furthermore, NEAT1 destabilized Apelin mRNA by recruiting UPF1. Apelin overexpression decreased HG- and IH-induced injury to HMEC-1 cells by activating the Nrf2/HO-1 pathway. Moreover, NEAT1 knockdown reduced HG- and IH-induced injury to HMEC-1 cells through Apelin. NEAT1 silencing reduced HMEC-1 cell injury through the Apelin/Nrf2/HO-1 signalling pathway in T2DM-OSA. Abbreviations: LncRNAs, long non-coding RNAs; T2DM, type 2 diabetes mellitus; OSA, obstructive sleep apnoea; NEAT1, nuclear paraspeckle assembly transcript 1; IH, intermittent hypoxia; HMEC-1, human microvascular endothelial cells; HG, high glucose; Nrf2, NF-E2-related factor 2; UPF1, up-frameshift suppressor 1; HO-1, haem oxygenase-1; qRT-PCR, quantitative real-time polymerase chain reaction; ELISA, enzyme-linked immunosorbent assay; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; TNF-α, tumour necrosis factor-α; CCK-8, Cell Counting Kit-8; IL-1β, interleukin-1β; ROS, reactive oxygen species; MDA, malondialdehyde; SOD, superoxide dismutase; RIP, RNA immunoprecipitation; SD, standard deviations; GSH, glutathione; AIS, acute ischaemic stroke; HMGB1, high mobility group box-1 protein; TLR4, toll-like receptor 4.

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“…These projections portend a future where more individuals are burdened by diabetes ( 5 ). Given that diabetes-associated vascular damage stands as the primary cause of mortality among T2DM patients, the imperative for enhanced predictive methodologies for these complications cannot be overstated ( 6 ).…”

Section: Introductionmentioning

confidence: 99%

Correlation of renal function indicators and vascular damage in T2DM patients with normal renal function

Zhang,

Gui,

Chen

et al. 2023

Front. Endocrinol.

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BackgroundThis study aimed to assess the correlation between renal function-related indices and vascular damages among patients with type 2 diabetes mellitus (T2DM) and normal renal function.MethodsWe screened a cohort of eligible patients with T2DM, ultimately including 826 individuals. Utilizing multifactorial logistic regression, we conducted an in-depth analysis to explore the potential associations between renal function-related indices—specifically BUN, Cr, ALB, ACR, and eGFR—and the incidence of diabetic vascular damage. Additionally, to comprehensively understand the relationships, we employed Spearman correlation analysis to assess the connections between these indicators and the occurrence of vascular damage.ResultsIn this cross-sectional study of 532 patients with carotid atherosclerosis (CA), the prevalence of CA was positively correlated with Cr (53.1%, 72.3%, 68.0%, P<0.05) and negatively correlated with eGFR (71.6%, 68.5%, 53.1%, P<0.05). the higher the Cr, the higher the predominance ratio of CA (T1: reference; T2:OR. 2.166,95%CI:1.454,3.225; T3:OR:1.677, 95%CI:1.075, 2.616; P<0.05), along with an eGFR of 66.9% and 52.0% in terms of sensitivity and specificity, with a 95% CI of 0.562-0.644.ConclusionWithin our experimental sample, a noteworthy observation emerged: Creatinine (Cr) exhibited a positive correlation with the prevalence of individuals affected by carotid atherosclerosis (CA), underscoring a potential connection between Cr levels and CA incidence. Conversely, the estimated Glomerular Filtration Rate (eGFR) demonstrated a negative correlation with the occurrence of CA, implying that lower eGFR values might be associated with an increased likelihood of CA development.

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Epigenetic basis of diabetic vasculopathy

Cited by 14 publications

References 159 publications

Metabolic memory: mechanisms and diseases

Metabolic memory: mechanisms and diseases

LncRNA NEAT1 aggravates human microvascular endothelial cell injury by inhibiting the Apelin/Nrf2/HO-1 signalling pathway in type 2 diabetes mellitus with obstructive sleep apnoea

Correlation of renal function indicators and vascular damage in T2DM patients with normal renal function

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