title: Melatonin protects against chronic intermittent hypoxia-induced cardiac hypertrophy by modulating autophagy through the 5' adenosine monophosphate-activated protein kinase pathway.
abstract: 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.
authors.affiliation: Department of Respiratory and Critical Care Medicine, Tongji Hospital, Huazhong University of Science and Technology, No.1095 Jiefang Ave, Wuhan 430030, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Xie
authors.affiliation: Department of Respiratory and Critical Care Medicine, Tongji Hospital, Huazhong University of Science and Technology, No.1095 Jiefang Ave, Wuhan 430030, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Department of Respiratory and Critical Care Medicine, Tongji Hospital, Huazhong University of Science and Technology, No.1095 Jiefang Ave, Wuhan 430030, China.
authors.forename: Yue-Ying
authors.initials: YY
authors.lastname: Pan
authors.affiliation: Department of Respiratory and Critical Care Medicine, Tongji Hospital, Huazhong University of Science and Technology, No.1095 Jiefang Ave, Wuhan 430030, China.
authors.forename: Zhi-Hua
authors.initials: ZH
authors.lastname: Wang
authors.affiliation: Department of Respiratory and Critical Care Medicine, Tongji Hospital, Huazhong University of Science and Technology, No.1095 Jiefang Ave, Wuhan 430030, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Ren
authors.affiliation: Department of Respiratory and Critical Care Medicine, Tongji Hospital, Huazhong University of Science and Technology, No.1095 Jiefang Ave, Wuhan 430030, China.
authors.forename: Xue-Ling
authors.initials: XL
authors.lastname: Guo
authors.affiliation: Department of Respiratory and Critical Care Medicine, Tongji Hospital, Huazhong University of Science and Technology, No.1095 Jiefang Ave, Wuhan 430030, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Yuan
authors.affiliation: Department of Respiratory and Critical Care Medicine, Tongji Hospital, Huazhong University of Science and Technology, No.1095 Jiefang Ave, Wuhan 430030, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Shang
authors.affiliation: Department of Respiratory and Critical Care Medicine, Tongji Hospital, Huazhong University of Science and Technology, No.1095 Jiefang Ave, Wuhan 430030, China. Electronic address: hgliu@tjh.tjmu.edu.cn.
authors.forename: Hui-Guo
authors.initials: HG
authors.lastname: Liu
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D006332:Cardiomegaly / Q000201:enzymology / Q000209:etiology / Q000517:prevention & control*; D002316:Cardiotonic Agents / Q000494:pharmacology; D002460:Cell Line; D002908:Chronic Disease; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D000860:Hypoxia / Q000150:complications*; D008297:Male; D008550:Melatonin / Q000494:pharmacology* / Q000502:physiology; D046529:Microscopy, Electron, Transmission; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D010588:Phagosomes / Q000187:drug effects / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D020181:Sleep Apnea, Obstructive / Q000150:complications
chemical_list: D002316:Cardiotonic Agents; D047428:Protein Kinase Inhibitors; D055372:AMP-Activated Protein Kinases; D008550:Melatonin
keywords: Adenosine monophosphate-activated protein kinase; Apoptosis; Autophagy; Cardiac hypertrophy; Chronic intermittent hypoxia