Astragaloside IV attenuates chronic intermittent hypoxia‐induced myocardial injury by modulating Ca²⁺ homeostasis

Abstract

Obstructive sleep apnea syndrome (OSAS) is an important consequence of chronic intermittent hypoxia (CIH). Astragaloside IV (AS‐IV) exerts multiple protective effects in diverse diseases. However, whether AS‐IV can attenuate CIH‐induced myocardial injury is unclear. In this study, rats exposed to CIH were established and treated with AS‐IV for 4 weeks. In vitro, H9C2 cardiomyocytes subjected to CIH exposure were treated with AS‐IV for 48 hours. Then the cardiac function, morphology, fibrosis, apoptosis and Ca2+ homeostasis were determined to assess cardiac damage. Results showed that AS‐IV attenuated cardiac dysfunction and histological lesions in CIH rats. The increased TUNEL‐positive cells and activated apoptotic proteins in CIH rats were reduced by AS‐IV. We also noticed that AS‐IV reversed the accumulation of Ca2+ and altered expressions of Ca2+ handling proteins (decreases of SERCA2a and RYR2, and increases of p‐CaMKII and NCX1) under CIH exposure. Furthermore, CIH‐induced reduction of SERCA2a activity was increased by AS‐IV in rats. Similar results were also observed in H9C2 cells. Altogether, these findings indicate that AS‐IV modulates Ca2+ homeostasis to inhibit apoptosis, protecting against CIH‐induced myocardial injury eventually, suggesting it may be a potential agent for cardiac damage of OSAS patients.Significance of the studyChronic intermittent hypoxia (CIH) is a great contributor of OSAS, which is closely associated with cardiovascular diseases. It is necessary for developing a promising drug to attenuate CIH‐induced myocardial injury. This work suggests that AS‐IV can attenuate myocardial apoptosis and calcium disruption, thus protecting against CIH‐induced myocardial injury. It may represent a novel therapeutic for cardiac damage of OSAS.

Banxia-Houpu decoction diminishes iron toxicity damage in heart induced by chronic intermittent hypoxia

“… 2019 ; Jiang et al. 2020 ), this study indicated that CIH-exposed mice showed pathological changes and fibrosis, which were also risk factors for cardiac dysfunction. Hence, it is necessary to undertake active prevention and treatment in the early stage of CIH.…”

Protective effect of Astragaloside IV on chronic intermittent hypoxia-induced vascular endothelial dysfunction through the calpain-1/SIRT1/AMPK signaling pathway

“…Capn1 −/− mice were also divided randomly into two groups ( n = 10): the control group (CK) and the chronic intermittent hypoxia group (MK). The model of CIH exposure established in this study was reported previously ( Jiang et al, 2020 ). Briefly, the mice were exposed to cages of automated, computer-controlled O 2 concentration exchange systems (Proox-100, Shanghai Tow-Int Tech Ltd.) to achieve a similar oxyhemoglobin saturation (SpO 2 ) nadir (50∼60%) in moderate to severe patients based on previous studies ( Zhou et al, 2014 ; Hu et al, 2021 ; Li et al, 2021 ).…”

“…Human coronary artery endothelial cells (HCAECs) were purchased from BLUEFBIO and grown in DMEM supplemented with 15% fetal bovine serum (HyClone, Logan, Utah, United States) in a CO 2 incubator as described previously ( Lv et al, 2019 ). The model of CIH in HCAECs was implemented by alternating cycles of 1% O 2 for 5 min followed by 20% O 2 for 5 min (3 cycles/h) at 37°C for 24 h in a chamber through automated, computer-controlled O 2 concentration exchange systems (GC-CT, Heilongjiang MAWORDE Industry and Trade Ltd.) as described previously ( Jiang et al, 2020 ; Xu H. et al, 2021 ; Yan et al, 2021 ). Cells were incubated with As-IV (100 µM), MDL-28170 (calpain-1 inhibitor, 20 µM) and SRT1720 (SIRT1 activator, 4 µM) for 48 h before CIH exposure.…”

“…Our previous studies demonstrated that As-IV protected against hyperglycemia-induced VED by inhibiting calpain-1 overactivation ( Nie et al, 2019 ). As-IV also attenuates CIH-induced myocardial injury and inflammation ( Chen et al, 2020 ; Jiang et al, 2020 ). However, the potential mechanism of As-IV activity against CIH-induced VED is not clear.…”

Deciphering the Efficacy and Mechanism of Astragalus membranaceus on High Altitude Polycythemia by Integrating Network Pharmacology and In Vivo Experiments

“…Anticoagulants and estrogen medications are currently commonly utilized to treat the condition [ 10 , 11 ], but their side effects, including renal failure, nausea, vomiting, dizziness, and exhaustion [ 12 ], are readily apparent. Recently, a number of natural compounds have demonstrated therapeutic potential for hypoxic illness [ 13 , 14 , 15 ]. They are easily accessible, have many physiological effects, and are non-toxic.…”