Transcriptome Analysis of Human Primary Endothelial Cells (HUVEC) from Umbilical Cords of Gestational Diabetic Mothers Reveals Candidate Sites for an Epigenetic Modulation of Specific Gene Expression

Within the complex pathological picture associated to diabetes, high glucose (HG) has "per se" effects on cells and tissues that involve epigenetic reprogramming of gene expression. In fetal tissues, epigenetic changes occur genome-wide and are believed to induce specific long term effects. Human umbilical vein endothelial cells (HUVEC) obtained at delivery from gestational diabetic women were used to study the transcriptomic effects of chronic hyperglycemia in fetal vascular cells using Affymetrix microarrays. In spite of the small number of samples analyzed (n=6), genes related to insulin sensing and extracellular matrix reorganization were found significantly affected by HG. Quantitative PCR analysis of gene promoters identified a significant differential DNA methylation in TGFB2. Use of Ea.hy926 endothelial cells confirms data on HUVEC. Our study corroborates recent evidences suggesting that epigenetic reprogramming of gene expression occurs with persistent HG and provides a background for future investigations addressing genomic consequences of chronic HG.