Noncoding RNAs in diabetes vascular complications

Beltrami, Cristina; Angelini, Timothy G.; Emanueli, Costanza

doi:10.1016/j.yjmcc.2014.12.014

Cited by 66 publications

(66 citation statements)

References 116 publications

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“…LncRNAs have been implicated in specifc physiological and pathological processes, including cardiovascular diseases [13,14]. A recent study of Greco et al [15] investigated lncRNAs deregulated in patients with non end-stage dilated hypokinetic ischemic cardiomyopathy.…”

Section: Discussionmentioning

confidence: 99%

WITHDRAWN: Downregulation of AC061961.2, LINGO1-AS1, and RP11-13E1.5 is associated with dilated cardiomyopathy progression

Qiu¹,

Ye²,

Yin³

et al. 2018

Oncotarget

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Purpose: This study aimed to explore lncRNAs implicated in dilated cardiomyopathy (DCM) using high-throughput sequencing.Methods: From February 2016 to May 2017, ten samples of failing hearts collected from the left ventricles of DCM patients undergoing heart transplants, and ten control samples obtained from normal heart donors were included in this study. After sequencing, raw data were processed, and differentially expressed genes (DEGs) and lncRNAs between samples from patients with DCM and controls were screened, followed by functional enrichment analysis and Weighted Gene Coexpression Network Analysis (WGCNA). Five key lncNRAs were validated through real-time PCR.Results: After processing sequence data, 1398 DEGs were identified between DCM and control groups, including 267 lncRNAs. WGCNA identified seven modules that were significantly correlated with DCM. The top 50 genes in the three modules (black, dark-green, and green-yellow) were significantly correlated with the DCM disease state. Four core enrichment lncRNAs, such as AC061961.2, LINGO1-AS1, and RP11-557H15.4, in the green-yellow module were associated with functions of neurotransmitter secretion. Five core enrichment lncRNAs, such as KB-1299A7.2 and RP11-13E1.5, in the black module co-regulated functions associated with the regulation of blood circulation and heart contraction. AC061961.2, LINGO1-AS1, and RP11-13E1.5 were confirmed to be downregulated in DCM tissues by real-time PCR.Conclusion: The present study suggests that downregulation of AC061961.2, LINGO1-AS1, and RP11-13E1.5 is associated with DCM progression, and these may serve as key diagnostic biomarkers and therapeutic targets for DCM.

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Section: Discussionmentioning

confidence: 99%

WITHDRAWN: Downregulation of AC061961.2, LINGO1-AS1, and RP11-13E1.5 is associated with dilated cardiomyopathy progression

Qiu¹,

Ye²,

Yin³

et al. 2018

Oncotarget

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“…miRNAs have been implicated as key elements playing crucial roles in the pathogenesis of diabetes-associated CVD, including endothelial dysfunction, angiogenesis, hypertrophy, and heart failure (Urbich et al, 2008;Leeper and Cooke, 2011;Hata, 2013;Beltrami et al, 2014;Arunachalam et al, 2015;Zhu and Leung, 2015). Several endothelial-specific miRNAs have been identified as regulators of cardiac and endothelial function and linked to the regulation of angiogenesis and the development of senescence and inflammation (Suárez and Sessa, 2009;Caporali et al, 2011;Staszel et al, 2011; The work was supported by National Priorities Research Program grants [4-910-3-244, 5-149-3-040, 6-428-3-113] from Qatar National Research Fund (a member of Qatar Foundation) and a Biomedical Research Program establishment grant.…”

Section: Introductionmentioning

confidence: 99%

Molecular Interplay between microRNA-34a and Sirtuin1 in Hyperglycemia-Mediated Impaired Angiogenesis in Endothelial Cells: Effects of Metformin

Arunachalam

Lakshmanan

Samuel

et al. 2015

Journal of Pharmacology and Experimental Therapeutics

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Impaired angiogenesis is a prominent risk factor that contributes to the development of diabetes-associated cardiovascular disease. MicroRNAs (miRNAs), small noncoding RNAs, are implicated as important regulators of vascular function, including endothelial cell differentiation, proliferation, and angiogenesis. In silico analysis and in vitro studies indicate that silent information regulator 1 (SIRT1) is a potential target for endothelial cell-specific miRNAs. In this study, we investigated the molecular crosstalk between miR-34a, the protein product of SIRT1 (sirtuin1), and the antidiabetic drug, metformin, in hyperglycemia-mediated impaired angiogenesis in mouse microvascular endothelial cells (MMECs). MMECs were cultured, transfected with either a miR-34a inhibitor or mimic in normal glucose (11 mM) or high glucose (HG, 40 mM) in the presence or absence of metformin. The expression of miR-34a, sirtuin1, and their signaling targets was evaluated. miR-34a expression is upregulated in a hyperglycemic milieu and parallels changes in the expression of sirtuin1, post-translational modification of endothelial nitric oxide synthase (phospho/acetylation), as well as an impairment in angiogenesis. The presence of metformin, or the inhibition of miR-34a using an anti-miR-34a inhibitor, increases the expression of sirtuin1 and attenuates the impairment in angiogenesis in HG-exposed MMECs. In contrast, overexpression of a miR-34a mimic prevents metformin-mediated protection. These data indicate that miR-34a, via the regulation of sirtuin1 expression, has an anti-angiogenic action in MMECs, which can be modulated by metformin. In summary, miR-34a represents both a target whereby metformin mediates its vasculoprotective actions and also a potential therapeutic target for the prevention/treatment of diabetic vascular disease.

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“…Diabetes mellitus is the most common metabolic disorder worldwide that has not been fully controlled (1)(2)(3). Medicinal Plants are highly accepted options for treatment of diabetes in some countries (4).…”

Section: Introductionmentioning

confidence: 99%

The Effect of Ethanolic Extract of Urtica dioica Leaves on High Levels of Blood Glucose and Gene Expression of Glucose Transporter 2 (Glut2) in Liver of Alloxan-Induced Diabetic Mice

et al. 2015

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Background: Urtica dioica L. (stinging nettle) has been accepted for decreasing blood glucose levels; however, the exact mechanism of its anti-hyperglycemic effect remains to be understood. Objectives: We aimed to examine the effects of ethanolic extract of stinging nettle leaves on blood glucose levels and gene expression of Glucose Transporter 2 (Glut2) in liver of alloxan-induced diabetic mice. Materials and Methods: Twenty-four male Naval medical research institute (NMRI) mice were randomly divided to three groups. The control group received saline (10 mL/kg, intraperitoneally) for eight days, the diabetic group received three days of injections of alloxan (200 mg/kg, intraperitoneally) followed by five days of injections of ethanol (20%), and the diabetic + nettle extract group received alloxan for three days followed by five days of injections of the nettle extract (150 mg/kg). Mice were weighed before and after treatments (on days one and nine). On day nine, mice were sacrificed, blood samples were collected for measuring glucose levels and liver was dissected to examine changes in the Glut2 gene expression with the semi-quantitative reverse-transcription-polymerase chain reaction (RT-PCR) method. Results:The results showed that the nettle extract significantly decreased high levels of blood glucose (P < 0.001). The nettle extract also had a preventive effect on decrease in body weight. In addition, the results showed that the Glut2 gene expression was increased in liver of diabetic mice (P < 0.05) and was significantly prevented by the nettle extract in diabetic + nettle extract group (P < 0.05). Conclusions: It can be concluded that the nettle extract can reduce blood glucose levels in diabetic mice, at least partly, by influencing the Glut2 gene expression in mice liver.

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Noncoding RNAs in diabetes vascular complications

Cited by 66 publications

References 116 publications

WITHDRAWN: Downregulation of AC061961.2, LINGO1-AS1, and RP11-13E1.5 is associated with dilated cardiomyopathy progression

WITHDRAWN: Downregulation of AC061961.2, LINGO1-AS1, and RP11-13E1.5 is associated with dilated cardiomyopathy progression

Molecular Interplay between microRNA-34a and Sirtuin1 in Hyperglycemia-Mediated Impaired Angiogenesis in Endothelial Cells: Effects of Metformin

The Effect of Ethanolic Extract of Urtica dioica Leaves on High Levels of Blood Glucose and Gene Expression of Glucose Transporter 2 (Glut2) in Liver of Alloxan-Induced Diabetic Mice

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