Floris, Ilaria (2014) Characterisation of molecular and phenotypic effects induced by Gestational Diabetes Mellitus (GDM) on endothelial cells and placenta tissue. Doctoral Thesis.
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Gestational diabetes mellitus (GDM) is characterised by maternal hyperglyceamia first recognised during pregnancy. GDM produces chronic foetal hyperglyceamia and expressional changes in foetal endothelial cells (ECs).
Epigenetic modulation of foetal endothelial genes by the intra-uterine environment has been proposed. MicroRNAs (miRs) inhibit the expression of their mRNA targets and have been implicated in diabetes-induced endothelial dysfunction. MiR-101 impairs EC in part via direct inhibition of the methyltransferase Enhancer of Zester Homolog2 (EZH2) which catalysed the trimethylation on lysine 27 of histone H3 (H3K27m3).
We aimed to characterize the molecular and functional impact of GDM on the foetal ECs derived from the umbilical cord vein (HUVECs).
HUVECs prepared from GDM or healthy pregnancies, were assessed for apoptosis, migration, and angiogenic capacity. GDM-HUVECs showed decreased functional capacities, increased miR-101, reduced EZH2 and H3K27m3 expression. In GDM-HUVECs, miR-101 inhibition increased EZH2 expression, improved survival and endothelial functions. Moreover, cultured healthy-HUVECs were exposed to high (25mM, HG) or normal (5mM) D-glucose concentrations for 48 hours before being assessed for the aforementioned assay and for miR-101 and EZH2 expression. Similarly to GDM, in vitro HG impaired healthy-HUVEC function and elicited a concomitant increased in miR-101.
In conclusion GMD and HG impair HUVEC functions in part also via miR-101 upregulation.
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