OSM mitigates post-infarction cardiac remodeling and dysfunction by up-regulating autophagy through Mst1 suppression.
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. MI model was induced using left anterior descending coronary artery (LAD) ligation. In addition, cultured neonatal mouse cardiomyocytes were subjected to simulated MI. Our results revealed that OSM alleviated left ventricular remodeling, promoted cardiac function, restored mitochondrial cristae density and architecture disorders after 4weeks of MI. Enhanced autophagic flux was indicated in cardiomyocytes transduced with Ad-GFP -LC3 in the OSM treated group as compared with the MI group. OSM receptor Oβ knockout blocked the beneficial effects of OSM in postinfarction cardiac remodeling and cardiomyocytes autophagy. OSM pretreatment significantly alleviated left ventricular remodeling and dysfunction in Mst1 transgenic mice, while it failed to reverse further the postinfarction left ventricular dilatation and cardiac function in the Mst1 knockout mice. Our data revealed that OSM alleviated postinfarction cardiac remodeling and dysfunction by enhancing cardiomyocyte autophagy. OSM holds promise as a therapeutic target in treating HF after MI through Oβ receptor by inhibiting Mst1 phosphorylation.
Department of Cardiology, Tangdu Hospital, Fourth Military Medical University, Xi'an, China; Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Jianqiang
J
Hu
Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Lei
L
Zhang
Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Zhijing
Z
Zhao
Department of Cardiology, Tangdu Hospital, Fourth Military Medical University, Xi'an, China; Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Mingming
M
Zhang
Department of Cardiology, Tangdu Hospital, Fourth Military Medical University, Xi'an, China; Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Jie
J
Lin
Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Jiaxing
J
Wang
Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Wenjun
W
Yu
Department of Cardiology, Tangdu Hospital, Fourth Military Medical University, Xi'an, China; Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Wanrong
W
Man
Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Congye
C
Li
Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Rongqing
R
Zhang
Center for Translational Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania, USA.
Erhe
E
Gao
Department of Cardiology, Tangdu Hospital, Fourth Military Medical University, Xi'an, China; Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China. Electronic address: wanghc@fmmu.edu.cn.
Haichang
H
Wang
Department of Cardiology, Tangdu Hospital, Fourth Military Medical University, Xi'an, China; Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China. Electronic address: wintersun3@gmail.com.
Dongdong
D
Sun
D000818:Animals; D001343:Autophagy; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D053683:Oncostatin M / Q000235:genetics / Q000378:metabolism*; D053681:Oncostatin M Receptor beta Subunit / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D018487:Ventricular Dysfunction, Left / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020257:Ventricular Remodeling
D053681:Oncostatin M Receptor beta Subunit; C508352:Osm protein, mouse; C508349:Osmr protein, mouse; D011518:Proto-Oncogene Proteins; C082332:macrophage stimulating protein; D053683:Oncostatin M; D017228:Hepatocyte Growth Factor
Autophagy; Heart failure, HF; Mammalian Ste20-like kinase 1, Mst1; Myocardial infarction, MI; Oncostatin M, OSM