Melatonin alleviates postinfarction cardiac remodeling and dysfunction by inhibiting Mst1

Jianqiang Hu, Lei Zhang, Yang Yang, Yanjie Guo, Yanhong Fan, Mingming Zhang, Wanrong Man, Erhe Gao, Wei Hu, Russel J Reiter, Haichang Wang, Dongdong Sun

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

Melatonin reportedly protects against several cardiovascular diseases including ischemia/reperfusion (I/R), atherosclerosis, and hypertension. The present study investigated the effects and mechanisms of melatonin on cardiomyocyte autophagy, apoptosis, and mitochondrial injury in the context of myocardial infarction (MI). We demonstrated that melatonin significantly alleviated cardiac dysfunction after MI. Four weeks after MI, echocardiography and Masson staining indicated that melatonin notably mitigated adverse left ventricle remodeling. The mechanism may be associated with increased autophagy, reduced apoptosis, and alleviated mitochondrial dysfunction. Furthermore, melatonin significantly inhibited Mst1 phosphorylation while promoting Sirt1 expression after MI, which indicates that Mst1/Sirt1 signaling may serve as the downstream target of melatonin. We thus constructed a MI model using Mst1 transgenic (Mst1 Tg) and Mst1 knockout (Mst1-/-) mice. The absence of Mst1 abolished the favorable effects of melatonin on cardiac injury after MI. Consistently, melatonin administration did not further increase autophagy, decrease apoptosis, or alleviate mitochondrial integrity and biogenesis in Mst1 knockout mice subjected to MI injury. These results suggest that melatonin alleviates postinfarction cardiac remodeling and dysfunction by upregulating autophagy, decreasing apoptosis, and modulating mitochondrial integrity and biogenesis. The attributed mechanism involved, at least in part, Mst1/Sirt1 signaling.

Original languageEnglish (US)
JournalJournal of Pineal Research
DOIs
StateAccepted/In press - 2016

Keywords

  • Autophagy
  • Mammalian Ste20-like kinase 1
  • Melatonin
  • Myocardial infarction
  • Silent information regulator 1

ASJC Scopus subject areas

  • Endocrinology

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    Hu, J., Zhang, L., Yang, Y., Guo, Y., Fan, Y., Zhang, M., Man, W., Gao, E., Hu, W., Reiter, R. J., Wang, H., & Sun, D. (Accepted/In press). Melatonin alleviates postinfarction cardiac remodeling and dysfunction by inhibiting Mst1. Journal of Pineal Research. https://doi.org/10.1111/jpi.12368