TFPIα alleviated vascular endothelial cell injury by inhibiting autophagy and the class III PI3K/Beclin-1 pathway

Abstract

Endothelium (EC) dysfunction plays an important role in vascular diseases, such as arteriosclerosis and hypoxia/reoxygenation (H/R) injury. Tissue factor pathway inhibitor (TFPI) is the only physiological inhibitor of the TF/FVIIa complex in vivo. This experiment aimed to determine the effect of TFPIα on H/R-induced EC injury and the possible mechanisms. The MIC101 hypoxia system was used to establish an EC H/R injury model in vitro. Our results showed that 6 h after reoxygenation, the EC injury in H/R group was higher than that in the control group, whereas after adding TFPIα, the EC injury was alleviate than that in H/R group. The level of ROS was higher in the H/R group than in the control group, while it was apparently lower in the H/R+TFPIα group than in the H/R group. After H/R, the number of autophagosomes and the autophagic flux were significantly increased, whereas TFPIα could decrease the autophagy level after H/R. The expressions of LC3-II/LC3-I, Beclin-1 and PI3K were obviously higher after H/R and lower after adding TFPIα. In conclusion, autophagy contributes to EC injury during the H/R period. TFPIα could decrease autophagy in ECs, and the mechanism might be class III PI3K/Beclin-1 pathway regulation.