Macrophage stimulating 1-induced inflammation response promotes aortic aneurysm formation through triggering endothelial cells death and activating the NF-κB signaling pathway.

Aortic aneurysm formation is associated with endothelial cells dysfunction through an undefined mechanism. Macrophage stimulating 1 (Mst1) and NF-κB signaling pathway have been found to be related to inflammation response in endothelial cell damage. The goal of our study is to explore the role of Mst1 in regulating endothelial cell viability with a focus on NF-κB signaling pathway and inflammation response. Endothelial cell viability and death were determined immunofluorescence and ELISA. Agonist of NF-κB signaling pathway and siRNA against Mst1 were used. The results in our study demonstrated that Mst1 transcription and expression were significantly elevated after exposure to oxidative stress in endothelial cells. Once loss of Mst1 through transfection of siRNA (si-Mst1), endothelial cell viability and survival rate were rapidly increased in response to oxidative stress. In addition, we also found that Mst1 controlled inflammation response and mitochondrial function in endothelial cells. Re-activation of NF-κB signaling pathway was followed by an activation of inflammation response and mitochondrial dysfunction, as evidenced by increased expression of inflammation factors and decreased ATP synthesis. Altogether, our results identify Mst1 as the primary factors responsible for endothelial cells dysfunction in aneurysms formation through inducing inflammation response, endothelial apoptosis, and NF-κB signaling pathway activation.