Melatonin protects against the pathological cardiac hypertrophy induced by transverse aortic constriction through activating PGC-1β: In vivo and in vitro studies.

Abstract

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 C57BL/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.

• Authors: Mengen Zhai, Zhenhua Liu, Bin Zhang, Lin Jing, Buying Li, Kaifeng Li, Xiuju Chen, Meng Zhang, Bo Yu, Kai Ren, Yang Yang, Wei Yi, Jian Yang, Jincheng Liu, Dinghua Yi, Hongliang Liang, Zhenxiao Jin, Russel J Reiter, Weixun Duan, Shiqiang Yu
• Journal: Journal of pineal research (J Pineal Res) Vol. 63 Issue 3 (Oct 2017) ISSN: 1600-079X [Electronic] England
• PMID: 28708271 (Publication Type: Journal Article)
• Copyright: © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Chemical References

• Antioxidants
• Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
• Ppargc1a protein, mouse
• Angiotensin II
• Melatonin

Topics

• Angiotensin II
• Animals
• Antioxidants (pharmacology, therapeutic use)
• Cardiomegaly (metabolism, pathology, prevention & control)
• Disease Models, Animal
• Drug Evaluation, Preclinical
• Fibrosis
• Heart (drug effects)
• Lung Diseases (prevention & control)
• Male
• Melatonin (pharmacology, therapeutic use)
• Mice, Inbred C57BL
• Myocardium (metabolism, pathology)
• Myocytes, Cardiac (drug effects)
• Oxidative Stress (drug effects)
• Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha (metabolism)
• Primary Cell Culture
• Transcriptional Activation (drug effects)