High glucose-induced dysfunction of endothelial cells can be restored by HoxA9EC.

BACKGROUND

High glucose (HG)-induced endothelial dysfunction is a common pathologic process of vascular disease in patients with diabetes. HoxA9EC is a transcriptional regulator of genes involved in the stabilization of endothelial function. We sought to elucidate the effect of HG on HoxA9EC expression in human umbilical venous endothelial cells (HUVECs), and the potential role of HoxA9EC in antagonizing HG-induced endothelial dysfunction.

METHODS

HUVECs treated with HoxA9EC transfection were cultured in media with HG, and those treated either by HG or HoxA9EC knockdown were incubated without HG. These cells were then subjected to experiments including mRNA expression analysis for eNOS, VEGFR-2, and HoxA9EC by quantitative RT-PCR; protein level analysis for eNOS, VEGFR-2, and HoxA9EC by Western blot; detection of nitric oxide (NO) concentration; and migration assay.

RESULTS

Expression levels of eNOS, VEGFR-2, and HoxA9EC, as well as cell migration and NO concentration, decreased rapidly in HUVECs with HoxA9EC knockdown or under HG conditions. Overexpression of HoxA9EC significantly repaired expression of eNOS and VEGFR-2, cell migration, and NO release of endothelial cells under HG conditions.

CONCLUSIONS

Inhibition of HoxA9EC induced by HG contributed to endothelial cell dysfunction, which could be rescued by augmentation of HoxA9EC under HG conditions.