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Melatonin protects against the pathological cardiac hypertrophy induced by transverse aortic constriction through activating PGC ‐1β: In vivo and in vitro studies
Author(s) -
Zhai Mengen,
Liu Zhenhua,
Zhang Bin,
Jing Lin,
Li Buying,
Li Kaifeng,
Chen Xiuju,
Zhang Meng,
Yu Bo,
Ren Kai,
Yang Yang,
Yi Wei,
Yang Jian,
Liu Jincheng,
Yi Dinghua,
Liang Hongliang,
Jin Zhenxiao,
Reiter Russel J.,
Duan Weixun,
Yu Shiqiang
Publication year - 2017
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/jpi.12433
Subject(s) - melatonin , medicine , endocrinology , pressure overload , muscle hypertrophy , atrial natriuretic peptide , oxidative stress , downregulation and upregulation , fibrosis , biology , biochemistry , cardiac hypertrophy , gene
Melatonin, a circadian molecule secreted by the pineal gland, confers a protective role against cardiac hypertrophy induced by hyperthyroidism, chronic hypoxia, and isoproterenol. However, its role against pressure overload‐induced cardiac hypertrophy and the underlying mechanisms remains elusive. In this study, we investigated the pharmacological effects of melatonin on pathological cardiac hypertrophy induced by transverse aortic constriction ( TAC ). Male C57 BL /6 mice underwent TAC or sham surgery at day 0 and were then treated with melatonin (20 mg/kg/day, via drinking water) for 4 or 8 weeks. The 8‐week survival rate following TAC surgery was significantly increased by melatonin. Melatonin treatment for 8 weeks markedly ameliorated cardiac hypertrophy. Compared with the TAC group, melatonin treatment for both 4 and 8 weeks reduced pulmonary congestion, upregulated the expression level of α‐myosin heavy chain, downregulated the expression level of β‐myosin heavy chain and atrial natriuretic peptide, and attenuated the degree of cardiac fibrosis. In addition, melatonin treatment slowed the deterioration of cardiac contractile function caused by pressure overload. These effects of melatonin were accompanied by a significant upregulation in the expression of peroxisome proliferator‐activated receptor‐gamma co‐activator‐1 beta ( PGC ‐1β) and the inhibition of oxidative stress. In vitro studies showed that melatonin also protects against angiotensin II ‐induced cardiomyocyte hypertrophy and oxidative stress, which were largely abolished by knocking down the expression of PGC ‐1β using small interfering RNA . In summary, our results demonstrate that melatonin protects against pathological cardiac hypertrophy induced by pressure overload through activating PGC ‐1β.