Protective effect of Astragaloside IV on chronic intermittent hypoxia-induced vascular endothelial dysfunction through the calpain-1/SIRT1/AMPK signaling pathway
Fang Zhao, Yan Meng, Yue Wang, Siqi Fan, Yu Liu, Xiangfeng Zhang, Chenyang Ran, Hongxin Wang, Meili Lu
Abstract
Vascular endothelial dysfunction (VED) is linked with the pathogenesis of obstructive sleep apnea (OSA) comorbidities, such as cardiovascular disease. Astragaloside IV (As-IV) has exhibited significant improvement for endothelial dysfunction. Nonetheless, the protective mechanism is not clear. Therefore, the present study investigated the potential mechanism of As-IV on VED. Calpain-1 knockout and wild-type C57BL/6 mice exposed to chronic intermittent hypoxia (CIH) were established and treated with As-IV (40, 80 mg/kg) for 4 weeks. Human coronary artery endothelial cells (HCAECs) subjected to CIH exposure were pretreated with As-IV, MDL-28170 (calpain-1 inhibitor) and SRT1720 (SIRT1 activator) for 48 h in vitro . The endothelial function, inflammation, oxidative stress and mitochondrial function were measured to evaluate VED. Our data revealed that As-IV treatment ameliorated CIH-induced endothelial-dependent vasomotion and augmented nitric oxide (NO) production. As-IV administration suppressed the secretion of inflammation, oxidative stress and mitochondrial dysfunction. As-IV treatment reduced the expression of calpain-1 and restored the downregulated expression of SIRT1 and Thr 172 AMPK and Ser 1177 eNOS phosphorylation. The effects of calpain-1 knockout and SRT1720 were similar to the effect of As-IV on VED. These findings demonstrated that As-IV ameliorated VED induced by chronic intermittent hypoxia via the calpain-1/SIRT1/AMPK signaling pathway.