scholarly journals Gestational diabetes induces alterations of sirtuins in fetal endothelial cells

2015 ◽  
Vol 79 (5) ◽  
pp. 788-798 ◽  
Author(s):  
Juan Gui ◽  
Arne Potthast ◽  
Anne Rohrbach ◽  
Katja Borns ◽  
Anibh M. Das ◽  
...  
2018 ◽  
Vol 132 (22) ◽  
pp. 2437-2449 ◽  
Author(s):  
Jasmin Strutz ◽  
Silvija Cvitic ◽  
Hubert Hackl ◽  
Karl Kashofer ◽  
Hannah M. Appel ◽  
...  

MicroRNAs (miRNAs), small non-coding RNAs, have emerged as important, epigenetic regulators of endothelial function. Metabolic disturbances such as diabetes alter miRNA expression. In adults, the miRNA transcriptome as well as endothelial function differ between the sexes. Here, we hypothesized that metabolic disturbances associated with gestational diabetes (GDM) alter miRNA signatures in feto-placental endothelial cells (fpEC), dependent on fetal sex. We isolated human primary fpEC after normal and GDM-complicated pregnancies with male and female neonates and screened for differential miRNA expression using next-generation miRNA sequencing. To test for miRNAs commonly regulated in fpEC of female and male progeny, data were stratified for fetal sex and maternal body mass index (BMI). Analyses were also performed separately for female and male fpEC, again accounting for maternal BMI as covariate. Potential biological pathways regulated by the altered set of miRNAs were determined using mirPath software. Maternal GDM altered 26 miRNA signatures when male and female fpEC were analyzed together. Separate analysis of male versus female fpEC revealed 22 GDM affected miRNAs in the females and only 4 in the males, without overlap. Biological functions potentially modulated by the affected miRNAs related to ‘Protein Processing in Endoplasmic Reticulum’ and ‘Proteoglycans in Cancer’. Maternal GDM alters miRNA signatures in fpEC, and biological functions affected by these miRNAs relate to well-known adverse functional consequences of diabetes on endothelium. GDM effects were highly dependent on fetal sex with miRNA signatures in female fpEC being more susceptible to metabolic derangements of GDM than miRNAs in male fpEC.


Diabetologia ◽  
2018 ◽  
Vol 61 (11) ◽  
pp. 2398-2411 ◽  
Author(s):  
Silvija Cvitic ◽  
Boris Novakovic ◽  
Lavinia Gordon ◽  
Christine M. Ulz ◽  
Magdalena Mühlberger ◽  
...  

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Mariangela Ucci ◽  
Pamela Di Tomo ◽  
Federica Tritschler ◽  
Vincenzo G. P. Cordone ◽  
Paola Lanuti ◽  
...  

Diabetes is associated with vascular inflammation, endothelial dysfunction, and oxidative stress, promoting the development of cardiovascular diseases (CVD). Several studies showed that a carotenoid-rich diet is associated to a reduced cardiovascular risk in healthy and diabetic subjects, although the mechanisms of action are still unknown. Here, the potential role of β-carotene (BC) and lycopene (Lyc) in human endothelial cells isolated from human umbilical cord vein (HUVECs) of women with gestational diabetes (GD) and respective controls (C) has been investigated. Results showed that BC and Lyc reduced the tumor necrosis factor alpha- (TNF-α-) stimulated monocyte-endothelium interaction (adhesion assay), membrane exposure (flow cytometry), and total expression levels (Western blot) of VCAM-1 and ICAM-1 in both cell types. Moreover, the treatment with BC and Lyc reduced the TNF-α-induced nuclear translocation of NF-κB (image flow cytometry) by preserving bioavailability of nitric oxide (NO, flow cytometry, and cGMP EIA kit assay), a key vasoactive molecule. Notably, BC and Lyc pretreatment significantly reduced peroxynitrite levels (flow cytometry), contributing to the redox balance protection. These results suggest a new mechanism of action of carotenoids which exert vascular protective action in diabetic condition, thus reinforcing the importance of a carotenoid-rich diet in the prevention of diabetes cardiovascular complications.


2014 ◽  
Vol 22 (3) ◽  
pp. 358-366 ◽  
Author(s):  
Julia Knabl ◽  
Rebecca Hüttenbrenner ◽  
Stefan Hutter ◽  
Maria Günthner-Biller ◽  
Christina Riedel ◽  
...  

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
P. Popova ◽  
L. Vasilyeva ◽  
A. Tkachuck ◽  
M. Puzanov ◽  
A. Golovkin ◽  
...  

Our aim was to study the expression of adipokine-encoding genes (leptin, adiponectin, and angiopoietin-like protein 4 (ANGPTL4)) in human umbilical vein endothelial cells (HUVECs) and adipokine concentration in cord blood from women with gestational diabetes mellitus (GDM) depending on glycaemic targets. GDM patients were randomised to 2 groups per target glycaemic levels: GDM1 (tight glycaemic targets, fasting blood glucose < 5.1 mmol/L and <7.0 mmol/L postprandial, N=20) and GDM2 (less tight glycaemic targets, <5.3 mmol/L and < 7.8 mmol/L, respectively, N=21). The control group included 25 women with normal glucose tolerance. ANGPTL4 expression was decreased in the HUVECs from GDM patients versus the control group (23.11 ± 5.71, 21.47 ± 5.64, and 98.33 ± 20.92, for GDM1, GDM2, and controls; p<0.001) with no difference between GDM1 and GDM2. The level of adiponectin gene expression was low and did not differ among the groups. Leptin gene expression was undetectable in HUVECs. In cord blood, leptin/adiponectin ratio (LAR) was increased in GDM2 compared to controls and GDM1 (p=0.038) and did not differ between GDM1 and controls. Tight glycaemic targets were associated with normalisation of increased LAR in the cord blood. ANGPTL4 expression was downregulated in HUVECs of newborns from GDM mothers and was not affected by the intensity of glycaemic control.


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