Methylglyoxal-mediated alteration of gene expression in human endothelial cells

Endothelial dysfunction is an important factor in the development of vascular diseases such as atherosclerosis, hypertension and diabetes. Methylglyoxal (MG) is a highly reactive dicarbonyl metabolite that is an extremely toxic glucose degradation product with strong oxidative activity. MG is involved in the pathogenesis of vascular complications of diabetes. Several studies have reported increased MG levels in pathology models of vascular injury. The present study investigated the genome-wide transcriptional responses of human umbilical vein endothelial cells (HUVECs) exposed to MG by microarray gene expression profiling. As a result, we identified 1,624 genes that were 1.5-fold up-or down-regulated within 12 h of MG treatment. The differentially expressed genes that were dysregulated in many biological processes included inflammatory responses, cell cycle, apoptosis, and cell adhesion. These results demonstrate the MG induced genome-wide alterations in expression profile in human endothelial cells and indicate that MG may cause cytotoxicity and tissue injury in the human endothelium. The data supports the view that MG-stimulated changes in gene expression contribute to the development of vascular disease.