Bidirectional regulation role of PARP-1 in high glucose-induced endothelial injury

Loss of poly (ADP-ribose) polymerase-1 (PARP-1) has been found to slow the progression of diabetes and diabetic angiopathy. In our study, we found bidirectional regulation of PARP-1 in high glucose induced endothelial injury, which promoting repair at the early stage of injury and inhibiting repair at the late stage of injury. To further investigate the mechanism of PARP-1 regulation, we first examined the expression of PARP-1 in aortic tissues and cultured cells at early, middle, and late stages of injury, PARP-1 expression was significantly greater than that of control group. Overexpression of PARP-1 in HUVECs significantly reduced the number of apoptotic cells 12 h after high glucose injury, while reducing the level of reactive oxygen species (ROS)/malondialdehyde (MDA)/inducible nitric oxide synthase (iNOS), increasing the level of endothelial nitric oxide synthase (eNOS); however, when the injury extended to 3 days, the number of apoptosis in HUVECs overexpressing PARP-1 was significantly higher than that in the injury group, and the level of ROS/MDA/iNOS was significantly higher, while the secretion of eNOS was significantly lower. Similarly, PARP-1 inhibitors aggravate early damage and inhibit late damage. We found that PARP-1 promoted the activation of P53 and P53R2 in endothelial cells after 12 h of injury, and PARP-1 promoted the activation of P53 and caspas3 in endothelial cells after 3 days of injury. Therefore, we suggest that PARP-1 plays a dual regulatory role in promoting repair or aggravating injury.