TRAIL protects against endothelium injury in diabetes via Akt-eNOS signaling

- Our data provide the protective effects of TRAIL against diabetes-induced endothelial damage.
- We demonstrated that TRAIL inhibit oxidative stress and increased antioxidant enzymes expression.
- We demonstrated that TRAIL inhibit high glucose-induced endothelial cell apoptosis.
- The data showed that the protective effects of TRAIL are mediated by the PI3K/Akt/NO pathway.

Objective: Although some studies have suggested that tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) might be involved in atherosclerosis, its potential role in endothelial dysfunction and apoptosis has not been investigated. The aim of this study was to evaluate the impact of TRAIL on endothelium injury in diabetes and the underlying mechanism involved. Methods: Experimental diabetes was induced using streptozotocin in rats. Cohorts of diabetic rats received an intraperitoneal injection of recombinant TRAIL (rTRAIL) 20 μg per rat weekly for 6 weeks. Endothelial function was assessed by acetylcholine (Ach)-induced endothelium-dependent vasorelaxation using aortic rings. The antiapoptotic effects of TRAIL and its possible mechanisms were investigated in cultured human umbilical vein endothelial cells (HUVECs). Results: Experimental diabetes attenuated endothelial function, which was significantly improved by rTRAIL treatment (63.5 ± 4.62% vs. 78.4 ± 2.79%, P < 0.01). In cultured HUVECs, TRAIL suppressed high glucose-induced reactive oxygen species (ROS) production and cellular apoptosis, as well as the production of NADPH oxidase. Furthermore, the antiapoptotic actions of TRAIL were accompanied by Akt and endothelial nitric oxide synthase (eNOS) phosphorylation, as well as increased NO production. Conclusions: These findings indicate a novel role of TRAIL in the protection against vascular injury in diabetes. The protective effects of TRAIL are dependent on the activation of Akt-dependent eNOS signaling.