Methylglyoxal Down-Regulates the Expression of Cell Cycle Associated Genes and Activates the P53 Pathway in Human Endothelial Cells

Although methylglyoxal (MGO) has emerged as key mediator of diabetic microvascular complications, the influence of MGO on the vascular transcriptome has not thoroughly been assessed. This study addressed 1) to what extent MGO changes the endothelial transcriptome when endothelial cells are exposed to an inflammatory milieu, 2) what are the dominant pathways by which these changes occur and 3) to what extent is this normalized by carnosine, a putative scavenger of MGO. Using gene expression profiling analysis, we demonstrated that MGO initiates distinct transcriptional changes in cell cycle/apoptosis gene, which may explain MGO toxicity at high concentrations. MGO did not augment TNF-α induced inflammation. For microarray analysis, six groups were employed as defined by a 24-hour incubation with the following substances: HUVECs in pro-inflammatory media (12,5 ng/ml TNF-α) with 1-2) no MGO ± 20 mM CN 3-4) 400 µM MGO ± 20 mM CN 5-6) 800 µM MGO ± 20 mM CN. HUVECs incubated with only TNF-α (without MGO and CN) served as control. Total RNA was isolated from all groups followed by gene expression profiling using Affymetrix microarrays.