Astragaloside <scp>IV</scp> attenuates chronic intermittent hypoxia‐induced myocardial injury by modulating Ca<sup>2+</sup> homeostasis
Shan Jiang, Guangyu Jiao, Yunqiu Chen, Mingxin Han, X. Wang, Wenjuan Liu
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 Ca 2+ 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 Ca 2+ and altered expressions of Ca 2+ 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 Ca 2+ 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 study Chronic 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.