Author:
Zhao Fang,Meng Yan,Wang Yue,Fan Siqi,Liu Yu,Zhang Xiangfeng,Ran Chenyang,Wang Hongxin,Lu Meili
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 Thr172 AMPK and Ser1177 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.
Funder
National Natural Science Foundation of China
Subject
Pharmacology (medical),Pharmacology
Cited by
13 articles.
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