Alteration of endothelial function markers in women with gestational diabetes and their fetuses

Mordwinkin, Nicholas M.; Ouzounian, Joseph G.; Yedigarova, Larisa; Montoro, Martin; Louie, Stan G.; Rodgers, Kathleen E.

doi:10.3109/14767058.2012.736564

Cited by 65 publications

(58 citation statements)

References 30 publications

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“…There is also evidence indicating that women with GDM develop endothelial dysfunction during pregnancy (Knock et al 1997), and despite returning to NGT, endothelial dysfunction is still evident in women 1-year post GDM pregnancy (Pleiner et al 2007). Indeed, women with GDM have increased circulating sICAM1 and sVCAM1 levels (Mordwinkin et al 2013). My recent studies have also shown that the expression and secretion of markers of endothelial cell dysfunction are increased in adipose tissue from women with GDM (Lappas 2014b).…”

Section: Figurementioning

confidence: 80%

NOD1 expression is increased in the adipose tissue of women with gestational diabetes

Lappas¹

2014

Journal of Endocrinology

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Maternal peripheral insulin resistance and increased inflammation are two features of pregnancies, complicated by gestational diabetes mellitus (GDM). The nucleotide-binding oligomerisation domain (NOD) intracellular molecules recognise a wide range of microbial products, as well as other intracellular danger signals, thereby initiating inflammation through activation of nuclear factor kB (NFkB). The aim of this study was to determine whether levels of NOD1 and NOD2 are increased in adipose tissue of women with GDM. The effect of NOD1 and NOD2 activation on inflammation and the insulin signalling pathway was also assessed. NOD1, but not NOD2, expression was higher in omental and subcutaneous adipose tissues obtained from women with GDM when compared with those from women with normal glucose tolerance (NGT). In both omental and subcutaneous adipose tissues from NGTand GDM women, the NOD1 ligand g-D-glutamyl-meso-diaminopimelic acid (iE-DAP) significantly induced the expression and secretion of the pro-inflammatory cytokine interleukin 6 (IL6) and chemokine IL8; COX2 (PTGS2) gene expression and subsequent prostaglandin production; the expression and secretion of the extracellular matrix remodelling enzyme matrix metalloproteinase 9 (MMP9) and the gene expression and secretion of the adhesion molecules ICAM1 and VCAM1. There was no effect of the NOD2 ligand muramyl dipeptide on any of the endpoints tested. The effects of the NOD1 ligand iE-DAP were mediated via NFkB, as the NFkB inhibitor BAY 11-7082 significantly attenuated iE-DAP-induced expression and secretion of pro-inflammatory cytokines, COX2 gene expression and subsequent prostaglandin production, MMP9 expression and secretion and ICAM1 and VCAM1 gene expression and secretion. In conclusion, the present findings describe an important role for NOD1 in the development of insulin resistance and inflammation in pregnancies complicated by GDM.

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Section: Figurementioning

confidence: 80%

NOD1 expression is increased in the adipose tissue of women with gestational diabetes

Lappas¹

2014

Journal of Endocrinology

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“…IL-6, TNF-α, adipocyte fatty acid-binding protein (AFABP)] (Abell et al 2015). In Table 1, the main agents, involved in the GDM physiopathology, are reported (Qiu et al 2004;Lewandowski et al 2007;Mordwinkin et al 2013;Lappas 2014;Abell et al 2015;Iyidir et al 2015;.…”

Section: Physiopathologymentioning

confidence: 99%

Gestational diabetes: An overview with attention for developing countries

Schiavone

Putoto

et al. 2016

Endocrine Regulations

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Gestational diabetes mellitus (GDM) is defi ned as a glucose intolerance that occurs for the fi rst time or it is fi rst identifi ed during pregnancy. Th e GDM etiology is multifactorial. It has not completely been established yet and several known risk factors may contribute to its onset. To date, there are no shared guidelines on the management and follow-up, especially regarding the lowincome countries. In this paper, we describe the state of art about epidemiology, physiopathology, diagnosis, and management of GDM. Moreover, we focus on the current state in low income countries trying to outline basis for further research.

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“…10 It has been suggested that, similar to observations in adult diabetic patients, GDM induces fetal endothelial cell (EC) dysfunction. [13][14][15] The persistence of the phenotypic and molecular changes induced by GDM in utero might be responsible for the increased cardiovascular and type 2 DM risk in children. 12 In line with this hypothesis, in vivo or in vitro exposure to high d-glucose (HG) levels induces epigenetic changes that negatively affect endothelial function.…”

mentioning

confidence: 99%

Gestational Diabetes Mellitus Impairs Fetal Endothelial Cell Functions Through a Mechanism Involving MicroRNA-101 and Histone Methyltransferase Enhancer of Zester Homolog-2

Floris¹,

Descamps²,

Vardeu³

et al. 2015

ATVB

106

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Objective— Gestational diabetes mellitus (GDM) produces fetal hyperglycemia with increased lifelong risks for the exposed offspring of cardiovascular and other diseases. Epigenetic mechanisms induce long-term gene expression changes in response to in utero environmental perturbations. Moreover, microRNAs (miRs) control the function of endothelial cells (ECs) under physiological and pathological conditions and can target the epigenetic machinery. We investigated the functional and expressional effect of GDM on human fetal ECs of the umbilical cord vein (HUVECs). We focused on miR-101 and 1 of its targets, enhancer of zester homolog-2 (EZH2), which trimethylates the lysine 27 of histone 3, thus repressing gene transcription. EZH2 exists as isoforms α and β. Approach and Results— HUVECs were prepared from GDM or healthy pregnancies and tested in apoptosis, migration, and Matrigel assays. GDM-HUVECs demonstrated decreased functional capacities, increased miR-101 expression, and reduced EZH2- β and trimethylation of histone H3 on lysine 27 levels. MiR-101 inhibition increased EZH2 expression and improved GDM-HUVEC function. Healthy HUVECs were exposed to high or normal d -glucose concentration for 48 hours and then tested for miR-101 and EZH2 expression. Similar to GDM, high glucose increased miR-101 expression. Chromatin immunoprecipitation using an antibody for EZH2 followed by polymerase chain reaction analyses for miR-101 gene promoter regions showed that both GDM and high glucose concentration reduced EZH2 binding to the miR-101 locus in HUVECs. Moreover, EZH2-β overexpression inhibited miR-101 promoter activity in HUVECs. Conclusions— GDM impairs HUVEC function via miR-101 upregulation. EZH2 is both a transcriptional inhibitor and a target gene of miR-101 in HUVECs, and it contributes to some of the miR-101-induced defects of GDM-HUVECs.

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Alteration of endothelial function markers in women with gestational diabetes and their fetuses

Cited by 65 publications

References 30 publications

NOD1 expression is increased in the adipose tissue of women with gestational diabetes

NOD1 expression is increased in the adipose tissue of women with gestational diabetes

Gestational diabetes: An overview with attention for developing countries

Gestational Diabetes Mellitus Impairs Fetal Endothelial Cell Functions Through a Mechanism Involving MicroRNA-101 and Histone Methyltransferase Enhancer of Zester Homolog-2

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