Sphingomyelin synthase 2 promotes H2O2-induced endothelial dysfunction by activating the Wnt/β-catenin signaling pathway

• Published in: International journal of molecular medicine Vol. 42; no. 6; pp. 3344 - 3354
• Main Authors: Zhang, Panpan, Hua, Lingyue, Hou, Huan, Du, Xingyue, He, Zhiqiang, Liu, Menghan, Hu, Xiaojuan, Yan, Nianlong
• Format: Journal Article
• Language: English
• Published: Greece Spandidos Publications UK Ltd 01.12.2018; D.A. Spandidos
• Subjects: Antibiotics; Apoptosis; beta Catenin - metabolism; Biosynthesis; Blotting, Western; Cardiomyocytes; Cell Adhesion - drug effects; Cell cycle; Cell growth; Cell Line; Cell Proliferation - drug effects; Cell Proliferation - genetics; Cell Survival - drug effects; Cell Survival - genetics; Flow Cytometry; Human Umbilical Vein Endothelial Cells; Humans; Hydrogen Peroxide - toxicity; Kinases; L-Lactate Dehydrogenase - metabolism; Lipids; Malondialdehyde - metabolism; Oxidative stress; Phosphorylation; Proteins; Smooth muscle; Studies; Superoxide Dismutase - metabolism; Transferases (Other Substituted Phosphate Groups) - genetics; Transferases (Other Substituted Phosphate Groups) - metabolism; Wnt Signaling Pathway - drug effects; Beijing China; China; Israel
• ISSN: 1107-3756; 1791-244X
• DOI: 10.3892/ijmm.2018.3888

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 H2O2. In addition, these results demonstrated that SMS2 overexpression promoted apoptosis and macrophage adhesion of H2O2‑induced ECs, thereby increasing the expression of β‑catenin. Furthermore, SMS activity was inhibited with Dy105, combined with simultaneous treatment with LiCl or H2O2. 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.