Endothelin-1 Regulation Is Entangled in a Complex Web of Epigenetic Mechanisms in Diabetes

Biswas, Saumik; Feng, Biao; Thomas, Anoop; Chen, S; Aref‐Eshghi, Erfan; Sadiković, Bekim; Chakrabarti, Subrata

doi:10.33549/physiolres.933836

Cited by 23 publications

(12 citation statements)

References 48 publications

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“…It could be summarized that downregulation of MALAT1 reduced blood pressure, serum levels of ET-1, and vWF and MMP-9 expression in IA tissues. It has been suggested previously that downregulation of MALAT1 restrains the upregulation of the glucose-induced ET-1 transcription product [24]. Also, it is reported that ectopic MALAT1 expression is the inducer of vWF generation [25].…”

Section: Discussionmentioning

confidence: 87%

RETRACTED ARTICLE: Long Non-coding RNA MALAT1/microRNA-143/VEGFA Signal Axis Modulates Vascular Endothelial Injury-Induced Intracranial Aneurysm

Gao

Zhang

et al. 2020

Nanoscale Res Lett

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The roles of some long non-coding RNAs (lncRNAs) in intracranial aneurysm (IA) have been investigated in many studies. The aim of this study is to elucidate the mechanism of lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1)/microRNA-143 (miR-143)/vascular endothelial growth factor-A (VEGFA) signal axis in vascular endothelial injury-induced IA. MALAT1, miR-143, and VEGFA expression in IA tissues and normal arterial tissues were detected. Matrix metalloproteinase 9 (MMP-9) in tissues, von Willebrand factor (vWF) in serum and tissues, and endothelin-1 (ET-1) in serum were detected. The modeled IA rats were injected with silenced or overexpressed MALAT1 for detecting vascular endothelial injury. Vascular endothelial cells from patients with IA were abstracted and transfected with silenced or overexpressed MALAT1 to verify the impacts of MALAT1 on cell viability and apoptosis. The connections among MALAT1, miR-143, and VEGFA were verified by online prediction, luciferase activity, and RNA-pull down assays. Overexpression of MALAT1 and VEGFA and poor expression of miR-143 were found in IA tissues. Downregulation of MALAT1 inhibited blood pressure, the expression of ET-1, vWF, and MMP-9, as well as the apoptotic index of vascular endothelial cells of rats with IA. Downregulated MALAT1 inhibited apoptosis and promoted viability of vascular endothelial cells in IA. MALAT1 bound to miR-143 and miR-143 targeted VEGFA. This study suggests that MALAT1 elevates VEGFA expression through competitive binding to miR-143, thereby boosting apoptosis and attenuating viability of vascular endothelial cells in IA.

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Section: Discussionmentioning

confidence: 87%

RETRACTED ARTICLE: Long Non-coding RNA MALAT1/microRNA-143/VEGFA Signal Axis Modulates Vascular Endothelial Injury-Induced Intracranial Aneurysm

Gao

Zhang

et al. 2020

Nanoscale Res Lett

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“…In diabetic rats, overexpression of the lncRNA ANRIL promoted Vegf upregulation and increased angiogenesis via activation of NF-κB signalling (68). A recent study also demonstrated that knocking down ANRIL, MALAT1, and ZFAS1 prevented glucose-induced upregulation of ET-1 transcripts (69).…”

Section: The Emerging Role Of Long Non-coding Rnasmentioning

confidence: 94%

The vascular epigenome in patients with obesity and type 2 diabetes: opportunities for personalized therapies

et al. 2020

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Our genetic background provides limited information on individual risk of developing vascular complications overtime. New biological layers, namely epigenetic modifications, are now emerging as potent regulators of gene expression thus leading to altered transcriptional programs and vascular disease phenotypes. Such epigenetic modifications, defined as changes to the genome that do not involve changes in DNA sequence, are generally induced by environmental factors and poor lifestyle habits. Of note, adverse epigenetic signals acquired during life can be transmitted to the offspring thus leading to premature alterations of the epigenetic and transcriptional landscape eventually leading to early endothelial dysfunction and vascular senescence. Modifications of the epigenome play a pivotal role in the pathophysiology of cardiometabolic disturbances such as obesity and type 2 diabetes. In these patients, changes of DNA methylation and chromatin structure contribute to alter pathways regulating insulin sensitivity, glucose homeostasis, adipogenesis and vascular function. In this perspective, unveiling the ‘epigenetic landscape’ in cardiometabolic patients may help to identify new players implicated in obesity and diabetes-related vascular dysfunction and may pave the way for personalized therapies in this setting. In the present review, we discuss current knowledge of the epigenetic routes implicated in vascular damage and cardiovascular disease in patients with metabolic alterations.

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“…C2519A; Lonza, Walkersville, MD). As described previously (10,11,20,29,49,63,64), these cells were grown in complete EBM-2 medium (Lonza, Kirkland, WA) supplemented with EGM-2 SingleQuots (Lonza) and 10% fetal bovine serum. Prior to experimentation, cells were plated at a density of 4.3 ϫ 10 5 cells/mL and used between passages 4 and 5 to minimize variability.…”

Section: Methodsmentioning

confidence: 99%

Glucose-induced, duration-dependent genome-wide DNA methylation changes in human endothelial cells

Aref‐Eshghi

Biswas

Chen

et al. 2020

American Journal of Physiology-Cell Physiology

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DNA methylation, a critical epigenetic mechanism, plays an important role in governing gene expressions during biological processes such as aging, which is well known to be accelerated in hyperglycemia (diabetes). In the present study, we investigated the effects of glucose on whole genome DNA methylation in small [human retinal microvascular endothelial cells (HRECs)] and large [human umbilical vein endothelial cells (HUVECs)] vessel endothelial cell (EC) lines exposed to basal or high glucose-containing media for variable lengths of time. Using the Infinium EPIC array, we obtained 773,133 CpG sites (probes) for analysis. Unsupervised clustering of the top 5% probes identified four distinct clusters within EC groups, with significant methylation differences attributed to EC types and the duration of cell culture rather than glucose stimuli alone. When comparing the ECs incubated for 2 days versus 7 days, hierarchical clustering analyses [methylation change >10% and false discovery rate (FDR) <0.05] identified 17,354 and 128 differentially methylated CpGs for HUVECs and HRECs, respectively. Predominant DNA hypermethylation was associated with the length of culture and was enriched for gene enhancer elements and regions surrounding CpG shores and shelves. We identified 88 differentially methylated regions (DMRs) for HUVECs and 8 DMRs for HRECs (all FDR <0.05). Pathway enrichment analyses of DMRs highlighted involvement of regulators of embryonic development (i.e., HOX genes) and cellular differentiation [transforming growth factor-β (TGF-β) family members]. Collectively, our findings suggest that DNA methylation is a complex process that involves tightly coordinated, cell-specific mechanisms. Such changes in methylation overlap genes critical for cellular differentiation and embryonic development.

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Endothelin-1 Regulation Is Entangled in a Complex Web of Epigenetic Mechanisms in Diabetes

Cited by 23 publications

References 48 publications

RETRACTED ARTICLE: Long Non-coding RNA MALAT1/microRNA-143/VEGFA Signal Axis Modulates Vascular Endothelial Injury-Induced Intracranial Aneurysm

RETRACTED ARTICLE: Long Non-coding RNA MALAT1/microRNA-143/VEGFA Signal Axis Modulates Vascular Endothelial Injury-Induced Intracranial Aneurysm

The vascular epigenome in patients with obesity and type 2 diabetes: opportunities for personalized therapies

Glucose-induced, duration-dependent genome-wide DNA methylation changes in human endothelial cells

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