Department of Cardiology, Tangdu Hospital, Fourth Military Medical University, Xi'an, China; Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Biochim Biophys Acta Mol Basis Dis. 2017 Aug;1863(8):1951-1961. doi: 10.1016/j.bbadis.2016.11.004. Epub 2016 Nov 4.
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.
心力衰竭（HF）在全球的发病率和患病率正在迅速上升，这可能归因于近年来心肌梗死后 HF 的恶化。在这里，我们研究了肿瘤坏死因子样弱凋亡诱导因子（OSM）对梗死后心脏重构的影响及其相关机制。采用左前降支（LAD）结扎法建立 MI 模型。此外，还对培养的新生小鼠心肌细胞进行了模拟 MI 处理。我们的结果表明，OSM 可减轻左心室重构，改善心脏功能，恢复梗死后 4 周的线粒体嵴密度和结构紊乱。与 MI 组相比，转导 Ad-GFP -LC3 的心肌细胞中自噬流增强。OSM 受体 Oβ 敲除阻断了 OSM 在梗死后心脏重构和心肌细胞自噬中的有益作用。OSM 预处理可显著减轻 Mst1 转基因小鼠的左心室重构和功能障碍，但不能逆转 Mst1 敲除小鼠梗死后的左心室扩张和心脏功能。我们的数据表明，OSM 通过抑制 Mst1 磷酸化增强心肌细胞自噬，从而减轻梗死后的心脏重构和功能障碍。OSM 通过 Oβ 受体抑制 Mst1 磷酸化，有望成为 MI 后治疗 HF 的治疗靶点。
