Melatonin protects against chronic intermittent hypoxia-induced cardiac hypertrophy by modulating autophagy through the 5′ adenosine monophosphate-activated protein kinase pathway

• Published in: Biochemical and biophysical research communications 2015-09, Vol.464 (4), p.975-981
• Main Authors: Xie, Sheng, Deng, Yan, Pan, Yue-ying, Wang, Zhi-hua, Ren, Jie, Guo, Xue-ling, Yuan, Xiao, Shang, Jin, Liu, Hui-guo
• Format: Article
• Language: English
• Subjects: Adenosine monophosphate-activated protein kinase; AMP-Activated Protein Kinases - antagonists & inhibitors; AMP-Activated Protein Kinases - metabolism; Animals; Apoptosis; Autophagy; Autophagy - drug effects; Cardiac hypertrophy; Cardiomegaly - enzymology; Cardiomegaly - etiology; Cardiomegaly - prevention & control; Cardiotonic Agents - pharmacology; Cell Line; Chronic Disease; Chronic intermittent hypoxia; Disease Models, Animal; Enzyme Activation - drug effects; Humans; Hypoxia - complications; Male; Melatonin - pharmacology; Melatonin - physiology; Microscopy, Electron, Transmission; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - enzymology; Myocytes, Cardiac - pathology; Phagosomes - drug effects; Phagosomes - pathology; Protein Kinase Inhibitors - pharmacology; Rats; Rats, Sprague-Dawley; Signal Transduction - drug effects; Sleep Apnea, Obstructive - complications
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2015.06.149

Obstructive sleep apnea syndrome (OSAS) is usually associated with multiple cardiovascular disorders, including myocardial hypertrophy. Melatonin protects the heart from damaging conditions. However, whether melatonin alleviates heart damage induced by chronic intermittent hypoxia (CIH) is unknown. We investigated the melatonin-induced protective role of AMPK-regulated autophagy in the myocardium by exposing rats to CIH and treating them with melatonin or saline daily for six weeks. In vivo, CIH induced significant myocardial hypertrophy; this trend was strikingly reversed by melatonin. Moreover, AMPK activation and autophagy was enhanced, and the number of autophagosomes increased. CIH induced apoptosis of cardiomyocytes; this was significantly mitigated by melatonin. In vitro, CIH induced hypertrophic changes in cardiomyocytes; this effect was significantly reversed by melatonin. Autophagy decreased after AMPK inhibition, and we found that autophagy was required for the protective function of melatonin. Our results suggest that melatonin ameliorates cardiac hypertrophy caused by CIH by inducing autophagy via the AMPK pathway and by autophagy-regulated apoptosis. •CIH exposure induced significant cardiac hypertrophy in rats.•Melatonin strikingly reversed cardiac hypertrophy caused by CIH.•Melatonin ameliorated CIH-induced cardiac hypertrophy by inducing autophagy enhancement.•Melatonin induces autophagy enhancement through AMPK pathway.•Autophagy enhancement induced by melatonin reduces apoptosis in myocardium.