Loss of histone deacetylase 2 inhibits oxidative stress induced by high glucose via the HO-1/SIRT1 pathway in endothelial progenitor cells.

Chronic diabetic foot ulcer (DFU) is a major cause of disability and mortality in patients with diabetes. Dysfunctional endothelial progenitor cells (EPCs) play important roles in preventing vascular complications in these patients. Our results determined the elevated expression of histone deacetylase 2 (HDAC2) both in patients with DFU and in high glucose (HG) induced EPCs. In this study, HDAC2 siRNA (si-HDAC2) was transfected to investigate the effects of HDAC2 on EPCs. Cell proliferation decreased in HG-induced EPCs, but it was upregulated after si-HDAC2 transfection. Tube formation of EPCs also decreased with HG, which was reversed by si-HDAC2 transfection. Furthermore, inflammatory factors and reactive oxygen species (ROS) in EPCs were detected, showing that HG increased TNF-α, IL-1β, IL-6, and ROS production in EPCs. However, si-HDAC2 reversed these effects. These results indicate that HDAC2 inhibitor may resist HG-induced EPC injury. Finally, reduced expression of HO-1-Sirt1 signaling in HG-induced EPCs also was reversed by HDAC2 siRNA. In conclusion, these findings indicate that HDAC2 inhibitor may prevent impaired cell proliferation, tube formation, inflammation, and ROS production in high-glucose EPCs.