Sphingomyelin synthase 2 promotes H 2 O 2 -induced endothelial dysfunction by activating the Wnt/β-catenin signaling pathway

Abstract

Atherosclerosis (AS) is the primary cause of various cardiovascular and cerebrovascular diseases and has high morbidity and mortality rates. Oxidative stress-induced endothelial cells (ECs) dysfunction is the pathological basis of AS. In addition, sphingomyelin (SM) and the Wnt/β-catenin signaling pathway are considered to be closely associated with AS; however, the specific mechanism is not clear. Therefore, the present study investigated whether SM may induce ECs dysfunction through the Wnt/β-catenin signaling pathway. Firstly, a sphingomyelin synthase 2 (SMS2) overexpression cell model was constructed. It was identified that the expression of SMS2 was increased when ECs were treated with H 2 O 2 . In addition, these results demonstrated that SMS2 overexpression promoted apoptosis and macrophage adhesion of H 2 O 2 -induced ECs, thereby increasing the expression of β-catenin. Furthermore, SMS activity was inhibited with Dy105, combined with simultaneous treatment with LiCl or H 2 O 2 . This additionally confirmed that Dy105 significantly inhibited SMS activity and decreased the level of ECs dysfunction and β-catenin content; however, LiCl served a key role in activating the Wnt/β-catenin signaling pathway to promote ECs dysfunction. Collectively, these results suggested that SMS2 overexpression may promote ECs dysfunction by activating the Wnt/β-catenin signaling pathway, while Dy105 may inhibit the evolution of oxidative stress-induced dysfunction.