OSM mitigates post-infarction cardiac remodeling and dysfunction by up-regulating autophagy through Mst1 suppression
| Autor: | Jianqiang Hu, Dongdong Sun, Zhijing Zhao, Rongqing Zhang, Jiaxing Wang, Mingming Zhang, Lei Zhang, Haichang Wang, Jie Lin, Wanrong Man, Erhe Gao, Wenjun Yu, Congye Li |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Genetically modified mouse Cardiac function curve medicine.medical_specialty Myocardial Infarction Oncostatin M 030204 cardiovascular system & hematology Mice Ventricular Dysfunction Left 03 medical and health sciences 0302 clinical medicine Proto-Oncogene Proteins Internal medicine Autophagy medicine Animals Myocardial infarction Ventricular remodeling Molecular Biology Mice Knockout Oncostatin M Receptor beta Subunit Ventricular Remodeling biology Hepatocyte Growth Factor fungi medicine.disease 030104 developmental biology Endocrinology Heart failure Knockout mouse cardiovascular system biology.protein Molecular Medicine |
| Zdroj: | Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1863:1951-1961 |
| ISSN: | 0925-4439 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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