eNOS S-nitrosylation mediated OxLDL-induced endothelial dysfunction via increasing the interaction of eNOS with β‑catenin.

Protein S-nitrosylation plays an important role in the progression of cardiovascular diseases. eNOS can be S-nitrosylated in endothelial cells, and this modification reversibly attenuates enzyme activity. Under physiological conditions, eNOS directly interacts with β‑catenin. However, whether and how eNOS S-nitrosylation regulates the β‑catenin signal pathway and participates in endothelial dysfunction remains unknown. Here, we show that OxLDL induces the S-nitrosylation of eNOS, which enhances the interaction between eNOS and β‑catenin, transcriptional activity of β‑catenin, cell migration and adhesion molecule expression in endothelial cells. In addition, these effects are partially abolished after eNOS is mutated at Cys94 and Cys99, but not Cys441, in endothelial cells. Furthermore, OxLDL increases iNOS expression. The specific iNOS inhibitor 1400 W decreases eNOS S-nitrosylation and the association of eNOS and β‑catenin, thereby blocking the β‑catenin signal pathway to alleviate OxLDL-induced endothelial dysfunction. Taken together, OxLDL induces eNOS S-nitrosylation at Cys94 and Cys99 via an iNOS-dependent manner, which may increase β‑catenin activation and trigger endothelial injury. This study describes a novel mechanism of endothelial dysfunction. • OxLDL increases the association of eNOS with β‑catenin. • OxLDL can induce S-nitrosylation of eNOS at Cys94 and Cys99 and this effect is dependent on iNOS. • S-nitrosylation of eNOS at Cys94 and Cys99 contributes to OxLDL-induced endothelial dysfunction. • S-nitrosylation of eNOS at Cys94 and Cys99 is essential for eNOS binding to β‑catenin in OxLDL-treated endothelial cells. [ABSTRACT FROM AUTHOR]