Author + information
- 1Department of Cardiology, Tangdu Hospital, Fourth Military Medical University, Xi’an, China
- 2Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi’an, China
- 3Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi’an, China
- 4Department of Biomedical Engineering, Fourth Military Medical University, Xi’an, China
- 5Center for Translational Medicine, Temple University School of Medicine, Philadelphia, PA, USA
The incidence and prevalence of heart failure (HF) in the world are rapidly rising possibly attributed to the worsened HF following myocardial infarction (MI) in recent years. Here we examined the effects of oncostatin M (OSM) on postinfarction cardiac remodeling and the underlying mechanisms involved.
a MI model was constructed by the left anterior descending (LAD) coronary artery ligation. Western blot was used to detect the expressions of related proteins. Echocardiography and Masson staining were used to measure the cardiac function and cardiac remodeling.
Melatonin significantly alleviated cardiac dysfunction after MI. Four weeks after MI, echocardiography and Masson staining indicated that melatonin notably mitigated adverse left ventricle remodeling. 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.