Astragaloside IV protects cardiomyocytes from hypoxia-induced injury by down-regulation of lncRNA GAS5.

BACKGROUND Poor understanding of the regulatory mechanisms of astragaloside IV (AS-IV) in cardiovascular protection limits clinical application of AS-IV in heart failure. Hypoxia is an important stimulus in the progression of heart failure. We investigated the role of AS-IV in hypoxia-treated cardiomyoblast H9c2 cells. METHODS Cell viability and apoptotic cells in hypoxia-treated H9c2 cells were detected by CCK-8 assay and flow cytometry, respectively. Expression of proteins associated with proliferation and apoptosis was measured by Western blot. Then effects of AS-IV on hypoxia-induced cell injury were explored, and the alteration of lncRNA growth arrest specific 5 (GAS5) level under AS-IV treatment was determined by RT-qPCR. Whether AS-IV affected hypoxia-treated H9c2 cells via lncRNA GAS5 was subsequently testified. Besides, whether AS-IV regulated lncRNA GAS5 expression was via modulating the PI3K/mTOR pathway was investigated. RESULTS Hypoxia-induced decreasing cell viability, increasing apoptotic cells, and proteins associated with proliferation and apoptosis were all attenuated by AS-IV treatments. Then, we found that lncRNA GAS5 expression was down-regulated by AS-IV treatment, and AS-IV might affect hypoxia-stimulated H9c2 cells through lncRNA GAS5. Finally, we found that inhibition of PI3K/mTOR or mTOR could reverse the AS-IV-induced down-regulation of lncRNA GAS5 in H9c2 cells. CONCLUSION AS-IV protected H9c2 cells against hypoxia through down-regulating lncRNA GAS5. Besides, AS-IV might repress lncRNA GAS5 expression via activation of the PI3K/mTOR pathway.